Catheter apparatuses for modulation of nerves in communication with the pulmonary system and associated systems and methods

ABSTRACT

Devices, systems, and methods for the selective positioning of an intravascular neuromodulation device are disclosed herein. Such systems can include, for example, an elongated shaft and a therapeutic assembly carried by a distal portion of the elongated shaft. The therapeutic assembly is configured for delivery within a blood vessel. The therapeutic assembly can include a pre-formed shape and can be transformable between a substantially straight delivery configuration; and a treatment configuration having the pre-formed helical shape to position the therapeutic assembly in stable contact with a wall of the body vessel. The therapeutic assembly can also include a mechanical decoupler operably connected to the therapeutic assembly that is configured to absorb at least a portion of a force exerted on the therapeutic assembly by the shaft so that the therapeutic assembly maintains a generally stationary position relative to the target site.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.62/080,189, filed Nov. 14, 2014, U.S. Provisional Application No.62/080,248, filed Nov. 14, 2014, and U.S. Provisional Application No.62/082,638, filed Nov. 21, 2014, all of which are incorporated herein byreference in their entireties. Further, components and features ofembodiments disclosed in the applications incorporated by reference maybe combined with various components and features disclosed and claimedin the present application.

TECHNICAL FIELD

The present technology relates generally to modulation of nerves thatcommunicate with the pulmonary system (e.g., pulmonary neuromodulationor “PN”) and associated systems and methods. In particular, severalembodiments are directed to radio frequency (“RF”) ablation catheterapparatuses for intravascular modulation of nerves that communicate withthe pulmonary system and associated systems and methods.

BACKGROUND

Pulmonary hypertension is an increase in blood pressure in the pulmonaryvasculature. When portions of the pulmonary vasculature are narrowed,blocked, or destroyed, it becomes harder for blood to flow through thelungs. As a result, pressure within the lungs increases and makes ithard for the heart to push blood through the pulmonary arteries and intothe lungs, thereby causing the pressure in the arteries to rise. Also,because the heart is working harder than normal, the right ventriclebecomes strained and weak, which can lead to heart failure. While thereare pharmacologic strategies to treat pulmonary hypertension, there isno curative therapy other than lung transplantation. Thus, there is astrong public-health need for alternative treatment strategies.

BRIEF DESCRIPTION OF THE DRAWINGS

Many aspects of the present technology can be better understood withreference to the following drawings. The components in the drawings arenot necessarily to scale. Instead, emphasis is placed on illustratingclearly the principles of the present technology.

FIG. 1 is a partially-schematic view of a neuromodulation systemconfigured in accordance with an embodiment of the present technology.

FIG. 2A is an enlarged side view illustrating a therapeutic assembly ofthe catheter of FIG. 1 in a low-profile configuration configured inaccordance with an embodiment of the present technology.

FIG. 2B is a further enlarged cut-away view of a portion of thetherapeutic assembly of FIG. 2A configured in accordance with anembodiment of the present technology.

FIG. 2C is a cross-sectional end view taken along line 2C-2C in FIG. 2A.

FIG. 3A is an illustrative cross-sectional anatomical front view showingthe advancement of the catheter shown in FIG. 1 along an intravascularpath in accordance with an embodiment of the present technology.

FIG. 3B is a side view of the therapeutic assembly shown in FIG. 2Awithin the main pulmonary artery in a low-profile configurationconfigured in accordance with an embodiment of the present technology.

FIG. 3C is a side view of the therapeutic assembly shown in FIG. 2Awithin the main pulmonary artery in a deployed configuration configuredin accordance with an embodiment of the present technology.

FIG. 3D is a side view of the therapeutic assembly shown in FIG. 2Awithin the left pulmonary artery in a deployed configuration configuredin accordance with an embodiment of the present technology.

FIG. 3E is a side view of the therapeutic assembly shown in FIG. 2Awithin the right pulmonary artery in a deployed configuration configuredin accordance with an embodiment of the present technology.

FIG. 4 is an illustrative cross-sectional anatomical front view showingthe advancement of the catheter shown in FIG. 1 along anotherintravascular path in accordance with an embodiment of the presenttechnology.

FIG. 5 is a side view of a therapeutic assembly having a single wireelectrode configured in accordance with an embodiment of the presenttechnology.

FIGS. 6A-6B are schematic representations illustrating rotationaldirections of the therapeutic assembly as noted by opposite arrowdirections.

FIG. 7 is a schematic side view of a catheter having an inner sheathconfigured in accordance with an embodiment of the present technology.

FIGS. 8A-8B are side views of a catheter having an inner sheathpositioned within the left pulmonary artery configured in accordancewith an embodiment of the present technology.

FIG. 9 is a side view of a therapeutic assembly in a deployedconfiguration having an anchoring device positioned within the leftpulmonary artery configured in accordance with an embodiment of thepresent technology.

FIG. 10 is a side view of a therapeutic assembly in a deployedconfiguration having an anchoring device positioned within the leftpulmonary artery configured in accordance with an embodiment of thepresent technology.

FIG. 11 is a side view of a therapeutic assembly having an anchoringdevice (shown in cross-section) within the right pulmonary artery in adeployed configuration configured in accordance with an embodiment ofthe present technology.

FIG. 12 is a side view of a therapeutic assembly having an anchoringdevice within the right pulmonary artery in a deployed configurationconfigured in accordance with an embodiment of the present technology.

FIG. 13 is a side view of a therapeutic assembly having an extendableshaft within the left pulmonary artery in a deployed configurationconfigured in accordance with an embodiment of the present technology.

FIG. 14 is a side view of a therapeutic assembly mechanically isolatedfrom the shaft within the right pulmonary artery in a deployedconfiguration configured in accordance with an embodiment of the presenttechnology.

FIG. 15 is a side view of therapeutic assemblies in a deployedconfiguration configured in accordance with an embodiment of the presenttechnology.

FIG. 16 is a side view of a therapeutic assembly having an inflectionsection in a deployed configuration configured in accordance with anembodiment of the present technology.

FIG. 17A is a side view of a catheter in a low-profile state configuredin accordance with an embodiment of the present technology. A fewexemplary deployed states are shown in phantom lines for purposes ofillustration.

FIG. 17B is an enlarged side view of a portion of the distal portion ofthe catheter of FIG. 17A in a low-profile state configured in accordancewith an embodiment of the present technology.

FIG. 17C is a cross-sectional end view of the shaft shown in FIG. 17Btaken along the line 17C-17C.

FIG. 18A is a perspective view of a distal portion of a catheter in alow-profile state configured in accordance with an embodiment of thepresent technology.

FIG. 18B is an isolated, enlarged view of the treatment member of FIG.18A configured in accordance with an embodiment of the presenttechnology.

FIG. 18C is a side view of the distal portion of the catheter shown inFIG. 18A in a low-profile state configured in accordance with anembodiment of the present technology.

FIG. 18D is a side view of the distal portion of the catheter shown inFIG. 18A in a deployed state configured in accordance with an embodimentof the present technology.

FIG. 19 is a schematic representation of a magnetically-deformablecatheter system configured in accordance with an embodiment of thepresent technology.

FIG. 20 is a cross-sectional end view of a non-occlusive catheter systemshown deployed in a vessel and configured in accordance with anembodiment of the present technology.

FIG. 21 is a cross-sectional end view of a non-occlusive catheter systemshown deployed in a vessel and configured in accordance with anotherembodiment of the present technology.

FIG. 22A is an enlarged isometric view of a therapeutic assemblyconfigured in accordance with an embodiment of the present technology.

FIG. 22B is an enlarged partially schematic view of a distal portion ofa treatment device within a blood vessel in accordance with anembodiment of the present technology.

FIG. 23A is an enlarged isometric view of an electrode assemblyconfigured in accordance with another embodiment of the presenttechnology.

FIG. 23B is an enlarged partially schematic view of a distal portion ofa treatment device within a blood vessel in accordance with anotherembodiment of the present technology.

FIG. 23C is an enlarged partially schematic view of a distal portion ofa treatment device within a blood vessel in accordance with yet anotherembodiment of the present technology.

FIG. 24 is an enlarged partially schematic side view of a distal portionof a treatment device within a blood vessel in accordance with a furtherembodiment of the present technology.

FIG. 25 is an enlarged side view of a distal portion of a treatmentdevice within a blood vessel in accordance with yet another embodimentof the present technology.

FIG. 26 is an enlarged side view of a distal portion of a treatmentdevice within a blood vessel in accordance with a further embodiment ofthe present technology.

FIG. 27 is an enlarged side view of a distal portion of a treatmentdevice within a blood vessel in accordance with an additional embodimentof the present technology.

FIG. 28 is a block diagram illustrating a method of endovascularlymonitoring nerve activity in accordance with an embodiment of thepresent technology.

FIG. 29 is a block diagram illustrating a method of endovascularlymonitoring nerve activity in accordance with another embodiment of thepresent technology.

DETAILED DESCRIPTION

The present technology is directed to neuromodulation devices andassociated systems and methods. Some embodiments of the presenttechnology, for example, are directed to catheters and associatedsystems and methods for pulmonary neuromodulation (“PN”). Specificdetails of several embodiments of the technology are described belowwith reference to FIGS. 1-29. PN is the partial or completeincapacitation or otherwise effective disruption of nerves thatcommunicate with the pulmonary system. For example, PN may inhibit,reduce, and/or block neural communication along neural fibers (i.e.,efferent and/or afferent nerve fibers) innervating the pulmonaryvessels. Such incapacitation can be long-term (e.g., permanent or forperiods of months, years, or decades) or short-term (e.g., for periodsof minutes, hours, days, or weeks). PN is expected to efficaciouslytreat pulmonary hypertension. Subjects with pulmonary hypertensiongenerally have high blood pressure in the lung vasculature that may leadto heart failure and they may, for example, experience symptoms such asdyspnea (shortness of breath), syncope, fatigue, chest pain and/oredema, and/or other symptoms as well. PN using methods and/or devicesdescribed herein may provide a therapeutically beneficial reduction inone or more of these symptoms. Additionally, PN using the methods and/ordevices of the present technology may modulate the release ofcirculating mediators of the nervous system (e.g., the sympatheticnervous system) and/or neuroendocrine system, thereby providing systemicmodulation of such mediators and/or modulating the function of specificbody organs other than the lungs. For example, the lungs producesignificant quantities of catecholamines that affect heart rate, bloodpressure, blood glucose levels, etc., and PN using the methods and/ordevices of the present technology may increase or decrease the amount ofcatecholamines released from the lungs.

The catheters, systems and methods of the present technology may effectPN in and/or near one or more pulmonary vessels. As used herein,“pulmonary vessel(s)” include any blood vessel that is adjacent toand/or provides intravascular access proximate to neural pathways thatcommunicate with the pulmonary system. For example, pulmonary vesselscan include pulmonary veins and pulmonary arteries, such as the mainpulmonary artery (“MPA”), the bifurcated portion of the pulmonaryartery, the right pulmonary artery (“RPA”), the left pulmonary artery(“LPA”), segmental pulmonary arteries, and sub-segmental pulmonaryarteries. Other non-limiting examples of pulmonary vessels include theright ventricular outflow tract, pulmonary arterioles, and/or any branchand/or extension of any of the pulmonary vessels described above. Insome embodiments, the catheters, systems and methods of the presenttechnology may effect PN in and/or near one or more pulmonary arteries(pulmonary arterial neuromodulation or “PAN”). For example, the presenttechnology may effect neuromodulation at a distal portion of the MPAand/or in one or more branches (e.g., distal branches) of the MPA. Incertain embodiments, the present technology may effect neuromodulationat or near the pulmonary valve (e.g., to affect nerves above and/orbelow the pulmonary valve).

As used herein, the terms “distal” and “proximal” define a position ordirection with respect to the treating clinician or clinician's controldevice (e.g., a handle assembly). “Distal” or “distally” are a positiondistant from or in a direction away from the clinician or theclinician's control device. “Proximal” and “proximally” are a positionnear or in a direction toward the clinician or clinician's controldevice.

It is typically advantageous to at least generally maintain the positionof a neuromodulation unit relative to the surrounding anatomy during aneuromodulation treatment. For example, it can be advantageous to atleast generally maintain stable contact between a therapeutic element ofa neuromodulation unit and an inner wall of a body lumen (e.g., a bloodvessel, a duct, an airway, or another naturally occurring lumen withinthe human body) during a neuromodulation treatment. In an alternativeembodiment, it may be advantageous to maintain the position of thetherapeutic element at the center of the vessel lumen or in some cases,offset from the center of the vessel lumen by a particular distance.This can enhance control and/or monitoring of the treatment, reducetrauma to the body lumen, and/or have other advantages. In some cases,at least generally maintaining the position of a neuromodulation unitrelative to the target anatomy during a neuromodulation treatment can bechallenging. For example, certain organs and/or body tissues may move inresponse to respiration, cardiac contraction and relaxation, peristalticmovement within blood vessels, and patient movement. Such movement oforgans and other tissues in a patient's body can cause movement of acatheter shaft within a vessel or other disadvantageous relativemovement between a neuromodulation unit connected to the shaft and theanatomy at a target site. Moreover, it may be challenging to maintain adevice at the target site. For example, a pulmonary artery may generallybe tapered, which can make it difficult to securely deploy certaindevice configurations in that location.

Another difficulty may exist with respect to initial positioning of aneuromodulation unit. When a neuromodulation unit is initiallypositioned at a treatment location within a pulmonary vessel or otherbody lumen (e.g., a renal vessel), the position of the neuromodulationunit may be suboptimal. For example, a catheter and/or a sheath carryingthe catheter may be insufficiently flexible to match the curvature ofanatomy near the treatment location (e.g., the curvature of a pulmonaryartery between the MPA and the RPA and/or LPA). This may cause thecatheter and/or the sheath to enter the body lumen out of alignment witha longitudinal dimension or other feature of the body lumen. When aneuromodulation unit of a misaligned catheter is initially moved into anexpanded form, the neuromodulation unit may also be misaligned with thebody lumen. When a neuromodulation unit is misaligned, one or moretherapeutic elements of the neuromodulation unit may be out of contactor in poor contact with an inner wall of a body lumen, thereby resultingin suboptimal (or no) energy delivery to a target site. Even when theneuromodulation unit is sufficiently well aligned for treatment tobegin, misalignment and migration may occur later and disturb the wallcontact, potentially requiring the treatment to be aborted. Correctingmisalignment of a neuromodulation unit can be challenging when theneuromodulation unit remains directly attached to an associated shafttrapped at a sharp turn.

I. Selected Embodiments of Catheter Apparatuses

FIG. 1 is partially-schematic diagram illustrating a pulmonaryneuromodulation system 100 (“system 100”) configured in accordance withan embodiment of the present technology. The system 100 includes anintravascular catheter 110 operably coupled to an energy source orenergy generator 132 via a connector 130 (e.g., a cable). The catheter110 can include an elongated shaft 116 having a proximal portion 114 anda distal portion 118. The catheter 110 also includes a handle assembly112 at the proximal portion 114. The catheter 110 can further include atherapeutic assembly 104 carried by or affixed to the distal portion 118of the elongated shaft 116, and the therapeutic assembly 104 can haveone or more energy delivery elements 106 configured to modulate nervesat or near the treatment location. The elongated shaft 116 can beconfigured to intravascularly locate the therapeutic assembly 104 at atreatment location within a pulmonary artery, renal artery, or otherblood vessel, or in a non-vascular delivery, such as through theesophagus, a bronchus, or another naturally occurring body lumen of ahuman patient (for example, via a natural orifice transluminalendoscopic surgery (NOTES) procedure). In certain embodiments, anextracorporeal approach may be employed, such as by using extracorporealultrasound.

The energy generator 132 can be configured to generate a selected formand/or magnitude of energy for delivery to the treatment site via theenergy delivery elements 106 of the therapeutic assembly 104. Forexample, the energy generator 132 can include an energy source (notshown) configured to generate RF energy (e.g., monopolar and/or bipolar,pulsed and/or non-pulsed, intravascular or extravascular, etc.),microwave energy, optical energy, ultrasound energy (e.g.,intravascularly delivered ultrasound, extracorporeal ultrasound,high-intensity focused ultrasound (HIFU), etc.), direct heat energy,radiation (e.g., infrared, visible, gamma, etc.), or another suitabletype of energy. For embodiments having multiple independent energydelivery elements 106, energy can be delivered to all or a portion ofthe energy delivery elements 106 simultaneously or at different times.Different firing sequences may be used, as appropriate. As an example, asingle energy delivery element may be selected at a time, or acombination of certain energy delivery elements or all of the energydelivery elements may be selected at a time. Energy delivery elementsmay be fired sequentially or simultaneously and/or may be firedaccording to a particular algorithm and/or operator input. In someembodiments, the therapeutic assembly 104 and/or energy deliveryelements 106 can be configured for use with a source of cryotherapeuticenergy, and/or for use with a source of one or more chemicals, such asdrugs or other agents (e.g., to provide the cryotherapeutic energyand/or chemical(s) to a target site for PN). It is believed thatcryotherapeutic energy, for example, may be especially effective for PN,where air within the lungs may function as an insulator. Cryotherapeuticenergy may provide a relatively deep and/or uniform freezing of tissue.

In some embodiments, instead of or in addition to the energy deliveryelements 106, the therapeutic assembly 104 can include one or moresubstance delivery features (e.g., ports) to produce chemically basedneuromodulation by delivering one or more chemicals (e.g., guanethidine,one or more alcohols (e.g., ethanol), phenol, a neurotoxin (e.g.,vincristine)), and/or other suitable agents selected to alter, damage,or disrupt nerves. Additionally, in some embodiments the substancedelivery features can be configured to deliver one or more painmanagement agents (e.g., an anesthetic agent) to the treatment siteand/or one or more substances that enhance or otherwise control energydelivered by one or more energy delivery element 106 and/or effect nervesensitivity or activation. For example, in some embodiments thetherapeutic assembly 104 can include one or more puncture or piercingelements such as needles (not shown) having one or more inlet ports. Thepuncture or piercing elements can be configured, when deployed, toextend from the therapeutic assembly 104 into the vessel wall at thetreatment site to deliver one or more chemicals. In some embodiments,one or more puncture or piercing elements may be deployed and/orpositioned using x-ray fluoroscopy. In certain embodiments, thetherapeutic assembly 104 can include at least one expandable element(not shown), such as a balloon, a basket, or a wire cage, that isconfigured to carry one or more chemicals and release the chemical(s)once the expandable element is expanded and in apposition with thevessel wall. For example, in some embodiments a radially exteriorsurface of the expandable element can be coated with selectedchemical(s). In yet other embodiments, the expandable element can beconfigured to release the chemical(s) from an interior portion of theexpandable element when submitted to a predetermined force threshold(e.g., radial forces exerted by the vessel walls).

Furthermore, the energy generator 132 can be configured to control,monitor, supply, or otherwise support operation of the catheter 110. Forexample, a control mechanism, such as foot pedal 144, may be connected(e.g., pneumatically connected or electrically connected) to the energygenerator 132 to allow an operator to initiate, terminate and/or adjustvarious operational characteristics of the energy generator, such aspower delivery. In some embodiments, the energy generator 132 may beconfigured to provide delivery of a monopolar electric field via theenergy delivery element(s) 106. In such embodiments, one or more neutralor dispersive electrode 142 may be electrically connected to the energygenerator 132 and selectively positioned at a location within thepatient's body (e.g., at, near, or within the esophagus, a bronchus,etc.) and/or attached to the exterior of the patient (not shown). Thedispersive electrode 142 can be positioned to direct the appliedelectric field in a particular direction and/or towards or away from aparticular anatomical location. Also, it can be advantageous to positionthe dispersive electrode such that it does not interfere with the lineof sight of the imaging device.

In some embodiments, the system 100 includes a remote control device(not shown) that can be configured to be sterilized to facilitate itsuse within a sterile field. The remote control device can be configuredto control operation of the therapeutic assembly 104, the energygenerator 132, and/or other suitable components of the system 100. Forexample, the remote control device can be configured to allow forselective activation of the therapeutic assembly 104. In otherembodiments, the remote control device may be omitted and itsfunctionality may be incorporated into the handle 112 or energygenerator 132.

As shown in FIG. 1, the energy generator 132 can further include anindicator or display screen 136. The energy generator 132 can includeother indicators, including one or more LEDs, a device configured toproduce an audible indication, and/or other suitable communicativedevices. In the embodiment shown in FIG. 1, the display 136 includes auser interface configured to receive information or instructions from auser and/or provide feedback to the user. For example, the energygenerator 132 can be configured to provide feedback to an operatorbefore, during, and/or after a treatment procedure via the display 136.The feedback can be based on output from one or more sensors (not shown)associated with the therapeutic assembly 104 such as temperaturesensor(s), impedance sensor(s), current sensor(s), voltage sensor(s),flow sensor(s), chemical sensor(s), ultrasound sensor(s), opticalsensor(s), pressure sensor(s) and/or other sensing or monitoringdevices. In some embodiments, the sensors can be used to monitor ordetect the presence or location of target neural structures and/orassess the extent or efficacy of the treatment, as discussed in greaterdetail below with reference to FIGS. 22-29.

The system 100 can further include a controller 146 having, for example,memory (not shown) and processing circuitry (not shown). The memory andstorage devices are computer-readable storage media that may be encodedwith non-transitory, computer-executable instructions such as diagnosticalgorithm(s) 133, control algorithm(s) 140, and/or evaluation/feedbackalgorithm(s) 138. The control algorithms 140 can be executed on aprocessor (not shown) of the system 100 to control energy delivery tothe energy delivery elements 106. In some embodiments, selection of oneor more parameters of an automated control algorithm 140 for aparticular patient may be guided by diagnostic algorithms 133 thatmeasure and evaluate one or more operating parameters prior to energydelivery. The diagnostic algorithms 133 provide patient-specificfeedback to the clinician prior to activating the energy deliveryelements 106 which can be used to select an appropriate controlalgorithm 140 and/or modify the control algorithm 140 to increase thelikelihood of efficacious neuromodulation.

Although in the embodiment shown in FIG. 1 the controller 146 isincorporated into the energy generator 132, in other embodiments thecontroller 146 may be a separate component distinct from the energygenerator 132. For example, additionally or alternatively, thecontroller 146 can be a personal computer(s), server computer(s),handheld or laptop device(s), multiprocessor system(s),microprocessor-based system(s), programmable consumer electronic(s),digital camera(s), network PC(s), minicomputer(s), mainframecomputer(s), and/or any suitable computing environment.

In some embodiments, the energy source 132 may include a pump 150 orother suitable pressure source (e.g., a syringe) operably coupled to anirrigation port (not shown) at the distal portion 118 of the catheter110. In other embodiments, the pump 150 can be a standalone deviceseparate from the energy source 132. Positive pressure generated by thepump 150 can be used, for example, to push a protective agent (e.g.,saline) through the irrigation port to the treatment site. In yet otherembodiments, the catheter 110 can include an adapter (not shown) (e.g.,a luer lock) configured to be operably coupled to a syringe (not shown)and the syringe can be used to apply pressure to the shaft 116. In aparticular embodiment, the pump 150 or other suitable pressure sourcecan be configured to push one or more of the aforementioned deliverableagents through the irrigation port to the treatment site (e.g.,chemically-based neuromodulation agents, pain management agents,energy-enhancement/control agents, agents that affect nerve sensitivityor activation, etc.).

FIG. 2A is a side view of the therapeutic assembly 104 in a low-profileor delivery state in accordance with an embodiment of the presenttechnology. A proximal region 208 of the therapeutic assembly 104 can becarried by or affixed to the distal portion 118 of the elongated shaft116. For example, all or a portion (e.g., a proximal portion) of thetherapeutic assembly 104 can be an integral extension of the shaft 116.A distal region 206 of the therapeutic assembly 104 may terminatedistally with, for example, an atraumatic, flexible curved tip 214having an opening 212 at its distal end. In some embodiments, the distalregion 206 of the therapeutic assembly 104 may also be configured toengage another element of the system 100 or catheter 110.

FIG. 2B is an enlarged view of a portion of the therapeutic assembly 104of FIG. 2A, and FIG. 2C is a cross-sectional end view taken along line2C-2C in FIG. 2A. Referring to FIGS. 2A-2C together, the therapeuticassembly 104 can include the one or more energy delivery elements 106carried by a helical/spiral-shaped support structure 210. Thehelical/spiral support structure 210 can have one or more turns (e.g.,two turns, etc.). The energy delivery elements 106 can be RF electrodes,ultrasound transducers, cryotherapeutic cooling assemblies, direct heatelements or other therapeutic delivery elements. The energy deliveryelements 106, for example, can be separate band electrodes axiallyspaced apart along the support structure 210 (e.g., adhesively bonded,welded (e.g., laser bonded) or bonded by mechanical interference to thesupport structure 210 at different positions along the length of thesupport structure 210). In other embodiments, the therapeutic assembly104 may have a single energy delivery element 106 at or near the distalportion 118 of the shaft 116.

In embodiments including where the support structure 210 includes morethan one energy delivery element 106, the support structure 210 caninclude, for example, between 1 and 12 energy delivery elements (e.g., 1energy delivery element, 4 energy delivery elements, 10 energy deliveryelements, 12 energy delivery elements, etc.). In particular embodiments,the therapeutic assembly 104 can include an even number of energydelivery elements 106. In some embodiments, the energy delivery elements106 can be spaced apart along the support structure 210 every 1 mm to 50mm, such as every 2 mm to every 15 mm (e.g., every 10 mm, etc.). In thedeployed configuration, the support structure 210 and/or therapeuticassembly 104 can have an outer diameter between about 12 mm and about 20mm (e.g., between about 15 mm and about 18 mm). Additionally, thesupport structure 210 and energy delivery elements 106 can be configuredfor delivery within a guide catheter between 5 Fr and 9 Fr. In otherexamples, other suitable guide catheters may be used, and outerdimensions and/or arrangements of the catheter 110 can vary accordingly.

In some embodiments, the energy delivery elements 106 are formed from ametal, such as gold, platinum, alloys of platinum and iridium or othersuitable electrically conductive materials. The number, arrangement,shape (e.g., spiral and/or coil electrodes) and/or composition of theenergy delivery elements 106 may vary. Each of the individual energydelivery elements 106 can be electrically connected to the energygenerator 132 by a conductor or bifilar wire 300 (FIG. 2C) extendingthrough a lumen 302 (FIG. 2C) of the shaft 116 and/or support structure210. For example, the individual energy delivery elements 106 may bewelded or otherwise electrically coupled to corresponding energy supplywires 300, and the wires 300 can extend through the elongated shaft 116for the entire length of the shaft 116 such that proximal ends of thewires 300 are coupled to the handle 112 and/or to the energy generator132.

In a particular embodiment, the catheter 110 can include an electricalelement 211 (FIG. 2A) positioned along the shaft 116 between the energydelivery elements 106 and the proximal portion of the shaft 116. Theelectrical element 211 can be electrically coupled to the energydelivery elements 106 via their respective bifilar wires 300. Thecatheter 110 can include an additional bifilar wire (not shown) thatelectrically couples the electrical element 211 and the energy generator132. The additional bifilar wire, for example, can extend proximallyfrom the electrical element 211 through the shaft 116 such that theproximal end of the wire is coupled to the handle 112 and/or to thegenerator 132. In some embodiments, the electrical element 211 caninclude an analog-to-digital converter configured to receive an analogsignal from the energy generator 132 and transmit a digital signal tothe energy delivery elements 106. Use of an analog-to-digital convertercan be advantageous because, unlike analog signals, digital signals arenot susceptible to interference. In these and other embodiments, theelectrical element 211 can include a multiplexer configured toindependently transmit signals to and/or from one or more of the energydelivery elements. As discussed below with respect to sensing neuralactivity at the target nerves, neural activity from the target nervessensed by the catheter 110—for example, by contacts (e.g., the energydelivery elements) at the distal portion of the shaft 116—can bedigitized and similarly processed by the multiplexer and transmittedoptionally through the shaft 116. Including a multiplexer in thecatheter 110 may, in some embodiments, allow for sensing of cleansignals from nerves. Neural signals may be generated using stimulationor may, in some cases, not be generated using stimulation. Devicesdescribed herein (e.g., devices including hard-wired catheter electrodesand/or a multiplexer) may be used to sense with or without stimulating.

As shown in the enlarged cut-away view of FIG. 2B, the support structure210 can be a tube (e.g., a flexible tube) and the therapeutic assembly104 can include a pre-shaped control member 220 positioned within thetube. Upon deployment, the control member 220 can form at least aportion of the therapeutic assembly 104 into a deployed state (FIG.3C-3E). For example, the control member 220 can have a pre-setconfiguration that gives at least a portion of the therapeutic assembly104 a helical/spiral configuration in the deployed state (FIG. 3C-3E).In some embodiments, the control member 220 includes a tubular structurecomprising a Nitinol multifilar stranded wire with a lumen 222therethrough and sold under the trademark HELICAL HOLLOW STRAND™ (HHS),and commercially available from Fort Wayne Metals of Fort Wayne, Ind.The lumen 222 can define a passageway for receiving a guide wire (notshown) that extends proximally from the opening 212 (FIG. 2A) at the tip214 of the therapeutic assembly 104. In other embodiments, the controlmember 220 may be composed of different materials and/or have adifferent configuration. For example, the control member 220 may beformed from nickel-titanium (Nitinol), shape memory polymers,electro-active polymers or other suitable shape memory materials thatare pre-formed or pre-shaped into the desired deployed state.Alternatively, the control member 220 may be formed from multiplematerials such as a composite of one or more polymers and metals.

As shown in FIG. 2C, the support structure 210 can be configured to fittightly against the control member 220 and/or wires 300 to reduce spacebetween an inner portion of the support structure 210 and the componentspositioned therein. For example, the control member 220 and the innerwall of the support structure 210 can be in intimate contact such thatthere is little or no space between the control member 220 and thesupport structure 210. Such an arrangement can help to reduce or preventthe formation of wrinkles in the therapeutic assembly 104 duringdeployment. The support structure 210 may be composed of one or morepolymer materials such as polyamide, polyimide, polyether block amidecopolymer sold under the trademark PEBAX®, polyethylene terephthalate(PET), polypropylene, aliphatic, polycarbonate-based thermoplasticpolyurethane sold under the trademark CARBOTHANE®, ELASTHANE™ TPU, apolyether ether ketone (PEEK) polymer, or another suitable material thatprovides sufficient flexibility to the support structure 210.

In some embodiments, when the therapeutic assembly 104 and/or supportstructure 210 is in deployed configuration, the therapeutic assembly 104and/or support structure 210 preferably define a minimum width ofgreater than or equal to approximately 0.040 inches. Additionally, thesupport structure 210 and energy delivery elements 106 are configuredfor delivery within a guide catheter no smaller than a 5 French guidecatheter. In other examples, other suitable guide catheters may be used,and outer dimensions and/or arrangements of the catheter 110 can varyaccordingly.

Referring to FIG. 2A, the curved tip 214 can be configured to provide anexit (e.g., via the opening 212) for a guide wire that directs the guidewire away from a wall of a vessel or lumen at or near a treatmentlocation. As a result, the curved tip 214 can facilitate alignment ofthe therapeutic assembly 104 in the vessel or lumen as it expands fromthe delivery state shown in FIG. 2A. Furthermore, the curved tip 214 canreduce the risk of injuring a wall of the vessel or lumen when a distalend of a guide wire is advanced from the opening 212. The curvature ofthe tip 214 can be varied depending upon the particularsizing/configuration of the therapeutic assembly 104 and/or anatomy at atreatment location. In some embodiments, the tip 214 may also comprise aradiopaque marker and/or one or more sensors (not shown) positionedanywhere along the length of the tip 214. For example, in someembodiments, the tip 214 can include one or more layers of material(e.g., the same or different materials) and the radiopaque marker can besandwiched between two or more layers. Alternatively, the radiopaquemarker can be soldered, glued, laminated, or mechanically locked to theexterior surface of the tip 214. In other embodiments, the entire tip214 or a portion of the tip 214 can be made of or include a radiopaquematerial and/or the tip 214 can be coated with a radiopaque material.The tip 214 can be affixed to the distal end of the support structure210 via adhesive, crimping, over-molding, or other suitable techniques.

The flexible curved tip 214 can be made from a polymer material (e.g.,polyether block amide copolymer sold under the trademark PEBAX™), athermoplastic polyether urethane material (e.g., sold under thetrademarks ELASTHANE™ or PELLETHANE®), or other suitable materialshaving the desired properties, including a selected durometer. As notedabove, the tip 214 is configured to provide an opening for the guidewire, and it is desirable that the tip itself maintain a desiredshape/configuration during operation. Accordingly, in some embodiments,one or more additional materials may be added to the tip material tohelp improve tip shape retention. In one particular embodiment, forexample, about 5 to 30 weight percent of siloxane can be blended withthe tip material (e.g., the thermoplastic polyether urethane material),and electron beam or gamma irradiation may be used to inducecross-linking of the materials. In other embodiments, the tip 214 may beformed from different material(s) and/or have a different arrangement.For example, in some embodiments the tip 214 may be straight.

In some embodiments, the distal portion 118 of the catheter can includeone or more irrigation ports (not shown) configured to emit one or moreprotective agents (e.g., saline) before, during, and/or after energydelivery to cool the energy delivery elements and surrounding tissue.The irrigation port(s) may be located anywhere along the supportstructure 210 and/or distal portion 118 of the shaft 116. The irrigationport(s) can be in fluid connection with one or more correspondingirrigation lumens that extends proximally along the shaft 116 from theirrigation port to the handle 112 and/or energy generator 132. In someembodiments, the catheter can include multiple irrigation ports, all influid communication with a corresponding irrigation lumen. In particularembodiments, an irrigation lumen can be coupled to a pump 150 (seeFIG. 1) or syringe (not shown) to facilitate conveyance of theprotective agent along the irrigation lumen and irrigation of protectiveagent through the irrigation port(s).

II. Selected Delivery Embodiments

Referring to FIG. 3A, intravascular delivery of the therapeutic assembly104 can include percutaneously inserting a guide wire 115 within thevasculature at an access site (e.g., femoral (FIG. 3A), brachial,radial, axillary, jugular (see FIG. 4) or subclavian arteries or veins)and progressing the guidewire to the MPA. The lumen 222 (FIG. 2C) of theshaft 116 and/or therapeutic assembly 104 can be configured to receive aguide wire 115 in an over-the-wire or rapid exchange configuration. Asshown in FIG. 3B, the shaft 116 and the therapeutic assembly 104 (in thedelivery state) can then be advanced along the guide wire 115 until atleast a portion of the therapeutic assembly 104 reaches the treatmentlocation. As illustrated in FIGS. 3A and 4, a section of the proximalportion 114 of the shaft 116 can be extracorporeally positioned andmanipulated by the operator (e.g., via the actuator 128 shown in FIG. 1)to advance the shaft 116 through the intravascular path and remotelymanipulate the distal portion 118 of the shaft 116.

Image guidance, e.g., computed tomography (CT), fluoroscopy,intravascular ultrasound (IVUS), optical coherence tomography (OCT),intracardiac echocardiography (ICE), or another suitable guidancemodality, or combinations thereof, may be used to aid the clinician'spositioning and manipulation of the therapeutic assembly 104. Forexample, a fluoroscopy system (e.g., including a flat-panel detector,x-ray, or c-arm) can be rotated to accurately visualize and identify thetreatment site. In other embodiments, the treatment site can be locatedusing IVUS, OCT, and/or other suitable image mapping modalities that cancorrelate the treatment site with an identifiable anatomical structure(e.g., a spinal feature) and/or a radiopaque ruler (e.g., positionedunder or on the patient) before delivering the catheter 110. Further, insome embodiments, image guidance components (e.g., IVUS, OCT) may beintegrated with the catheter 110 and/or run in parallel with thecatheter 110 to provide image guidance during positioning of thetherapeutic assembly 104. For example, such image guidance componentscan be coupled to a distal portion of the catheter 110 to providethree-dimensional images of the vasculature proximate the site tofacilitate positioning or deploying the therapeutic assembly 104 withinthe pulmonary blood vessel.

Once the therapeutic assembly 104 is positioned at a treatment locationwithin a pulmonary artery, the guide wire 115 can be at least partiallyremoved (e.g., withdrawn) from or introduced (e.g., inserted) into thetherapeutic assembly 104 to transform or otherwise move the therapeuticassembly 104 to a deployed configuration. FIG. 3C is a side view of thetherapeutic assembly 104 shown in FIG. 2A within the main pulmonaryartery in a deployed configuration, FIG. 3D is a side view of thetherapeutic assembly 104 within the left pulmonary artery, and FIG. 3Eis a side view of the therapeutic assembly 104 within the rightpulmonary artery in accordance with an embodiment of the presenttechnology. As shown in FIGS. 3C-3E, in the deployed state, at least aportion of the therapeutic assembly 104 can be configured to contact aninner wall of a pulmonary artery and to cause a fully-circumferentiallesion without the need for repositioning. For example, the therapeuticassembly 104 can be configured to form a continuous or discontinuouslesion that is fully-circumferential within a single plane perpendicularto the longitudinal axis of the vessel (see, for example, FIG. 23A). Inother embodiments, the therapeutic assembly 104 can be configured toform a continuous or discontinuous lesion that wraps around thecircumference of the vessel (one or more times) along a particularlength of the vessel (e.g., generally non-circumferential atlongitudinal segments of the treatment location). In several of suchembodiments, the lesion can have a helical/spiral configuration. Thiscan facilitate precise and efficient treatment with a low possibility ofvessel stenosis. In other embodiments, the therapeutic assembly 104 canbe configured to form a partially-circumferential lesion or afully-circumferential lesion at a single longitudinal segment of thetreatment location. In some embodiments, the therapeutic assembly 104can be configured to cause therapeutically-effective neuromodulation(e.g., using ultrasound energy) without contacting a vessel wall.

As shown in FIGS. 3C-3E, in the deployed state, the therapeutic assembly104 defines a substantially helical/spiral structure in contact with thepulmonary artery wall along a helical/spiral path. One advantage of thisarrangement is that pressure from the helical/spiral structure can beapplied to a large range of radial directions without applying pressureto a circumference of the pulmonary vessel. Thus, thespiral/helically-shaped therapeutic assembly 104 is expected to providestable contact between the energy delivery elements 106 and thepulmonary vessel wall when the wall moves in any direction. Furthermore,pressure applied to the pulmonary vessel wall along a helical/spiralpath is less likely to stretch or distend a circumference of a vesselthat could thereby cause injury to the vessel tissue. Still anotherfeature of the expanded helical/spiral structure is that it may contactthe pulmonary vessel wall in a large range of radial directions andmaintain a sufficiently open lumen in the pulmonary vessel allowingblood to flow through the helix/spiral during therapy. In otherembodiments, the therapeutic assembly 104 can define a circularstructure (see, for example, FIG. 23A) in contact with the pulmonaryartery wall along a circular or fully-circumferential path.

In some procedures it may be necessary to adjust the positioning of thetherapeutic assembly 104 one or more times. For example, the therapeuticassembly 104 can be used to modulate nerves proximate the wall of themain pulmonary artery, the left pulmonary artery, and/or the rightpulmonary artery and/or any branch or extension, and/or other pulmonaryvessels or sites proximate to neural pathways in communication with thepulmonary system. Additionally, in some embodiments the therapeuticassembly 104 may be repositioned within the same pulmonary vessel or atthe same site multiple times within the same procedure. Afterrepositioning, the clinician may then re-activate the therapeuticassembly 104 to modulate the nerves.

Often times it may be advantageous to modulate nerves and/or electricalsignals at two or more locations within the body. As an example, onedevice may be used to modulate renal nerves, while another device isused to modulate electrical signals in the heart. As another example,pulmonary neuromodulation may be effected in one location in the body,while modulation of electrical signals may be effected in the heart(e.g., simultaneously or sequentially). In some embodiments, modulationmay result in denervation of one or more of the treated locations. Incertain embodiments, cardiac tissue (e.g., the right atrium of theheart) of a patient may be ablated to modulate electrical signals withinthe heart (e.g., preventing abnormal electrical signals from occurring),and one or more renal arteries of the patient may also be ablated tomodulate nerves proximate the renal artery or renal arteries (e.g.,nerves extending along the outside of the renal artery or renalarteries). The modulation of nerves and/or electrical signals may resultin a reduction in clinical symptoms of pulmonary hypertension. Two ormore different locations in the body may be modulated in the sameprocedure (at the same time or at different times) and/or in differentprocedures (e.g., one taking place immediately after the other has beencompleted, or days, weeks or months after the other has been completed).Additionally, different types of denervation may be employed in onepatient.

In some methods, mechanical devices may be used, such as a device (e.g.,an implant) that modulates blood flow, creates an anastomosis, and/oraffects baroreceptors. Such devices may be used alone (e.g., multiple ofthe same type of device in different locations), in combination witheach other, and/or in combination with devices that modulate nervesand/or electrical signals.

Although the embodiments shown in FIGS. 3C-3E show a deployedtherapeutic assembly 104 in a spiral/helically-shaped configuration, inother embodiments, the therapeutic assembly 104 and/or other portions ofthe therapeutic assembly 104 can have other suitable shapes, sizes,and/or configurations (e.g., bent, deflected, zig-zag, Malecot, etc.).Other suitable devices and technologies are described in, for example,U.S. patent application Ser. No. 12/910,631, filed Oct. 22, 2010; U.S.patent application Ser. No. 13/279,205, filed Oct. 21, 2011; U.S. patentapplication Ser. No. 13/279,330, filed Oct. 23, 2011; U.S. patentapplication Ser. No. 13/281,360, filed Oct. 25, 2011; U.S. patentapplication Ser. No. 13/281,361, filed Oct. 25, 2011; PCT ApplicationNo. PCT/US11/57754, filed Oct. 25, 2011; U.S. Provisional PatentApplication No. 61/646,218, filed May 5, 2012; U.S. patent applicationSer. No. 13/793,647, filed Mar. 11, 2013; U.S. Provisional PatentApplication No. 61/961,874, filed Oct. 24, 2013; and U.S. patentapplication Ser. No. 13/670,452, filed Nov. 6, 2012. All of theforegoing applications are incorporated herein by reference in theirentireties. Non-limiting examples of devices and systems include theSymplicity Flex™, the Symplicity Spyral™ multielectrode RF ablationcatheter, and the Arctic Front Advance™ cardiac cryoablation system.

FIG. 5 shows another embodiment of a therapeutic assembly 404 comprisinga support structure 410 defined by a single wire electrode 406. Forexample, the support structure 410 can be a unipolar single metal wire(e.g., Nitinol) that is pre-formed into a helical/spiral shape. Thesingle wire electrode 406 can have a continuous electrically conductivesurface along all or a significant part of its length such that it formsa continuous helical lesion around a complete or nearly complete turn ofthe spiral/helix. In some embodiments, the wire electrode 406 can have adiameter of between about 0.002 inches and about 0.010 inches (e.g.,about 0.008 inches). In other embodiments, the therapeutic assembly 404can include a “ground” electrode that is electrically insulated from thespiral at a more proximal portion of the spiral/helix (e.g., a bipolarconfiguration). The spiral/helix can have a constant diameter, or inother embodiments the spiral/helix can have a varying diameter. Forexample, spiral/helix can have a diameter that tapers in a distaldirection or a proximal direction. In other embodiments, the single wireelectrode has discrete dielectric coating segments that are spaced apartfrom each other to define discrete energy delivery elements between thedielectric coating segments. The single wire electrode can be made froma shape memory metal or other suitable material. Additionally, thecontrol algorithm 140 (FIG. 1) can be adjusted to account for theincreased surface area contact of the single wire electrode 406 suchthat sufficient ablation depths can be achieved without charring oroverheating the inner wall of the vessel.

In some embodiments, the single wire electrode 406 can be delivered withthe guide catheter (not shown) or an additional sheath (not shown) forprecise positioning and deployment. The guide catheter (not shown) canbe advanced and/or manipulated until positioned at a desired locationproximate the treatment site. The therapeutic assembly 404 can then beinserted through the guide catheter. In some embodiments, thetherapeutic assembly 404 expands into a helical/spiral shape immediatelyonce exiting a distal end of the guide catheter. In other embodiments,the single wire electrode 406 can be tubular and transforms into ahelical/spiral shape when a guide wire (placed therethrough) is removedin a proximal direction. In yet other embodiments, the therapeuticassembly 404 expands into a circular shape immediately once exiting adistal end of the guide catheter.

A. Rotation Devices and Methods

As shown in FIGS. 6A and 6B, the therapeutic assembly 104 can beconfigured to rotate about a longitudinal axis A when advanced distallyfrom the shaft 116 or retracted proximally from the shaft 116. Forexample, when the therapeutic assembly 104 is advanced distally, thespiral/helical structure can be rotated in a first direction, as shownby arrows D1 in FIG. 6A). Likewise, when the therapeutic assembly 104 isretracted proximally, the spiral/helical structure can rotate in asecond direction, as shown by arrows D2 in FIG. 6B. Such a rotationalfeature can be particularly advantageous in the pulmonary vessels,since, at least at the MPA and proximal portions of the LPA and RPA, thepulmonary vessels have relatively large diameters that can require alarge number of lesions to provide fully-circumferential coverage and/oreffective treatment. To compensate for this, effective treatment in thepulmonary vessels can often times require multiple rotations of thetherapeutic assembly 104 to reposition the therapeutic assembly 104 andachieve such a fully-circumferential lesion. Additionally, rotation ofthe therapeutic assembly 104 can aid in maneuvering the therapeuticassembly 104 through a turn in a vessel, such as when accessing a branchor segment of a larger vessel (e.g., accessing the LPA and RPA from theMPA).

FIG. 7 is a side view of another embodiment of a catheter configured inaccordance with the present technology. The catheter can include atherapeutic assembly 604 generally similar to the previously describedtherapeutic assembly 104 (referenced herein with respect to FIGS. 1-4).As shown in FIG. 7, the catheter includes an inner sheath 617 slidablypositioned within a guide catheter 616 between the guide catheter 616and the therapeutic assembly 604. In certain vessels, contact forcesbetween the therapeutic assembly 604 and the vessel wall can make itdifficult to rotate the therapeutic assembly 604 distally and/orproximally. Likewise, a catheter and/or a sheath carrying the cathetermay be insufficiently flexible to match the curvature of anatomy nearthe treatment location, such as the curvature of a pulmonary arterybetween the MPA and the RPA and/or LPA. This may cause the catheterand/or the sheath to enter the body lumen out of alignment with alongitudinal axis of the body lumen. Because of the inner sheath 617 ofthe present technology, the guide catheter 616 and the inner sheath 617can rotate along a central axis independently of one another. Moreover,the inner sheath 617 can be sufficiently flexible to de-couple at leastthe therapeutic assembly 604 (positioned within a relatively stablepulmonary vessel) from the catheter (e.g., the guide catheter 616)positioned within or nearer to the contracting and expanding heart. Thisfeature can be advantageous because, for example, when at least aportion of the catheter and/or shaft is positioned within the heart, theguide catheter 616 often time translates the pumping movement of theheart to the therapeutic assembly 604. In addition, the inner sheath 617can also selectively position the therapeutic assembly 604 relative tothe vessel wall. For example, in some embodiments it may be advantageousto position the therapeutic assembly 604 at a central location withinthe vessel lumen before, during, or after energy delivery.

FIGS. 8A and 8B show examples of various deployment configurations ofthe catheter with the inner sheath 617. As shown in FIG. 8A, the shaft616 can be advanced along the MPA just proximal to the ostium of the LPA(or RPA (not shown)). The inner sheath 617 (containing the therapeuticassembly 604) can then be advanced past the distal end of the shaft 616and into the LPA for deployment of the therapeutic assembly 604. Asshown in FIG. 8B, in some embodiments the shaft 616 can be advanced justdistal of the pulmonary valve. The inner sheath 617 can then be advancedpast the distal end of the shaft 616, past the bifurcation, and into theLPA for deployment of the therapeutic assembly 604.

B. Anchoring Devices and Methods

The PN systems and/or therapeutic assemblies discloses herein caninclude one or more anchoring devices for stabilizing the distal portionand/or therapeutic assembly relative to the vessel wall and/orselectively positioning the distal portion and/or therapeutic assemblyrelative to the vessel wall (e.g., at a central location within thevessel lumen, selectively offset from the center of the vessel lumen).

FIG. 9, for example, is a side view of another embodiment of a cathetershown in the deployed configuration within the LPA in accordance withthe present technology. The catheter can be generally similar to thepreviously described catheters 110 or (referenced herein with respect toFIGS. 1-7A). However, as shown in FIG. 9, the catheter includes fixationmembers 801 (shown schematically for illustrative purposes only) alongat least a portion of its shaft 816 and/or inner sheath 817. Thefixation members 801 can be configured to contact the inner wall of thepulmonary vessel and stabilize the distal portion 818 and/or therapeuticassembly 804 with respect to the pulmonary vessel. Such stabilizationcan be advantageous because the pulmonary vessels constantly move as aresult of the surrounding anatomy, particularly the contraction andrelaxation of the heart, and also the respiratory cycle. As previouslydiscussed, the most common intravascular approach to the pulmonaryvessel involves the positioning of at least a portion of the catheterand/or shaft within the heart. As a result, the shaft translates thepumping movement of the heart to the therapeutic assembly 804. Thefixation members 801 can stabilize at least the therapeutic assembly 804within the pulmonary vessel so that movement of the catheter (e.g., theshaft 816) will not affect the alignment and/or contact of thetherapeutic assembly 804 and the vessel wall. In some embodiments, thefixation members 801 can be atraumatic or non-tissue penetrating, and inother embodiments the fixation members 801 can be tissue-penetrating(e.g., embedded in the tissue by radial force). The fixation members 801can have any size or configuration suitable to stabilize the therapeuticassembly 804 relative to the vessel.

FIG. 10 is a side view of another embodiment of a catheter shown in thedeployed configuration within the LPA in accordance with the presenttechnology. The catheter can include an expandable inner sheath 901that, when in the deployed configuration, expands to an outer radiusgenerally equal to or greater than the inner radius of the vessel at thetarget location (e.g., a pulmonary vessel). As such, at least a distalend 903 of the sheath 901 can expand to engage the vessel wall therebyexerting a radially outward force against the vessel wall andstabilizing the sheath 901. In some embodiments, the sheath 901 cancomprise an expandable stent-like structure which is collapsed in adelivery state within the elongated shaft 916 and expanded to a deployedstate when advanced beyond a distal end 915 of the elongated shaft 916.Once deployed, the sheath 901 helps to mechanically isolate thetherapeutic assembly 904 from the shaft 916. The sheath 901 can have agenerally tapered shape such that the distal end 903 of the sheath 901has a greater diameter than a proximal end (not shown). In someembodiments, at least a portion of the sheath 901 can include one ormore fixation members configured to engage the vessel wall.

FIG. 11 is a side view of another embodiment of a catheter shown in thedeployed configuration within the RPA in accordance with the presenttechnology. The catheter can include a guide sheath 1006 and acircumferentially grooved or threaded elongated member 1010 slideablypositioned therethrough. As shown in FIG. 11, the elongated member 1010can be mated with an anchor 1002. Once deployed, the anchor 1002 can befixed or secured to the vessel wall by frictional force and/or fixationmembers (not shown) (see FIG. 9 and accompanying description). Inoperation, insertion of the catheter 1017 from its proximal end (notshown) causes the therapeutic assembly 1004 to rotate in a distaldirection while the anchor 1002 remains relatively generally stationary.In some embodiments (not shown), the anchor 1002 can be fixed to theguide sheath 1006.

FIG. 12 is a side view of another embodiment of a catheter shown in thedeployed configuration within the RPA in accordance with the presenttechnology. The catheter can include an expandable anchor 1101configured to expand against at least a portion of the vessel wall andsecure the therapeutic assembly 1104 relative to the local anatomy. Forexample, as shown in FIG. 12, once advanced distally past the cathetershaft 1106, the expandable anchor 1101 can expand and exert an outwardforce against the vessel wall. In particular embodiments, the anchor1101 can engage and/or exert a contact force in one or more branches ofthe pulmonary artery simultaneously. For example, as shown in theillustrated embodiment, the anchor 1101 can span the bifurcation of theMPA into the LPA and/or RPA. Additionally, the anchor 1101 can have atapered shape in the proximal and/or distal directions, and in otherembodiments, the anchor 1101 can have a relatively uniformcross-sectional area along its length. In yet other embodiments, theanchor 1101 can have a main body and one or more branches (not shown)configured to be positioned within at least a portion of the MPA and theLPA or RPA, respectively. In some embodiments, the expandable anchor1101 can be a stent, balloon, self-expanding basket or other suitableexpandable or shape-changing structures or devices.

C. Tension-Relieving Devices and Methods

FIG. 13 is a side view of another embodiment of the catheter having acollapsible inner shaft 1201 configured in accordance with an embodimentof the present technology. At least a proximal portion of thetherapeutic assembly 1204 can be carried by the inner shaft 1201. Asshown in FIG. 13, the inner shaft 1201 can have a “telescoping” designthat allows the inner shaft 1201 to extend and retract freely such thatproximal and distal movement of the shaft 1216 caused by the cardiaccycle, respiration, etc. will not pull or push the therapeutic assembly104 out of position. Instead such motion is absorbed by thecollapsible/extendable design of the inner shaft 1201. In someembodiments, the catheter can include a locking and/or activationmechanism (not shown) so that the timing and/or extent of theextension/retraction of the inner shaft 1201 can be controlled by theclinician. In further embodiments, the inner shaft can be corrugatedalong at least a portion of length to allow extension and retraction.Likewise, in a particular embodiment, the inner shaft 1201 can be abraided structure having a plurality of sections with alternatingflexibility (e.g., by altering wire diameter, wire count, etc.) As aresult, the sectioned inner shaft 1201 would allow for compression andextension with motion, thus mechanically isolating (at least in part)the therapeutic assembly 1204 from the shaft 1206.

FIG. 14 is a side view of another embodiment of the catheter having atherapeutic assembly 1304 mechanically isolated from the shaft 1316 byan isolating element 1315. The isolating element 1315 can include afirst portion 1303 operably connected to the therapeutic assembly 1304,a second portion 1305 operably connected to the shaft 1316, and aconnector 1301 therebetween. The connector 1301 can have enough slacksuch that the position of the therapeutic assembly 1304 with respect tothe vessel in which it is expanded is generally unaffected by movementof the shaft 1316. As discussed above, often times during cardiaccontraction and relaxation the movement of the shaft 1316 is strongenough to pull or push the therapeutic assembly 1304 along the pulmonaryvessel. For example, when the heart contracts, the shaft 1316 can bepulled distally by the contracting heart muscles, thereby pulling thetherapeutic assembly 1304 distally (and likely out of position). Theisolating element 1315 of the present technology mechanically isolatesthe therapeutic assembly 1304 from the catheter shaft 1316, allowing theshaft to move while the therapeutic assembly 1304 remains relativelystationary. In some embodiments, the catheter can include a lockingand/or activation mechanism 1307 operably connected to the isolatingmember 1315 so that the timing of the release of the therapeuticassembly 1304 from the shaft 1316 can be controlled by the clinician.Additional devices and deployment methods for mechanical isolation ofthe therapeutic assembly from the shaft and/or catheter can be found inU.S. patent application Ser. No. 13/836,309, filed Mar. 15, 2013, titled“CATHETERS HAVING TETHERED NEUROMODULATION UNITS AND ASSOCIATED DEVICES,SYSTEMS, AND METHODS,” which is incorporated herein by reference in itsentirety.

In some embodiments, the therapeutic assembly and/or support structurecan be modified to relieve tension between therapeutic assembly and theshaft. For example, as shown in FIG. 14, the support structure 1410 caninclude an extended segment 1401 at a proximal section of thehelical/spiral portion 1403 of the support structure 1410 and/ortherapeutic assembly 1404. Such an extension can provide more slack andgreater flexibility at the proximal section of the helical/spiralportion 1403. Additionally, one or more turns (labeled (1), (2), (3) and(4) in FIG. 14) can be added to the support structure 1410 to increaseflexibility and/or the lengthening potential of the therapeutic assembly1404. In a particular embodiment shown in FIG. 16, an inflection section1501 can be included along the generally straight portion of the supportstructure 1510. Similar to the features described above with referenceto FIG. 15, the inflection section 1501 can provide the added slack toabsorb the disruptive motion of the shaft 1516.

D. Additional Embodiments

FIG. 17A is a side view of a catheter apparatus 1700 (“catheter 1700”)configured in accordance with an embodiment of the present technology.The catheter 1700 can include a proximal portion 1702, a distal portion1704, a handle assembly 1706 at the proximal portion 1702, and anelongated shaft 1710 extending distally from the handle assembly 1706.The distal portion 1704 of the elongated shaft 1710 can include anactuatable portion 1716 and one or more energy delivery elements 1712(e.g., electrodes). For example, as shown in FIG. 17A, the catheter 1700can include a single energy delivery element 1712 positioned at adistal-most portion of the shaft 1710. In other embodiments, thecatheter 1700 can include more than one energy delivery element 1712and/or one or more energy delivery elements 1712 can be positioned atany location along the length of the shaft 1710.

The handle assembly 1706 can include a control 1708 that is electricallycoupled to the actuatable portion 1716 at the distal portion 1704 of theshaft 1710. For example, the catheter 1700 can include one or more wires(not shown in FIG. 17A) extending distally from the handle assembly 1706through or along the shaft to the actuatable portion 1716. As indicatedby arrow A, movement of the actuatable portion 1716 by the control 1708can deflect, flex and/or bend the distal portion 1704 of the shaft 1710to space the energy delivery element 1712 apart from a longitudinal axisL of the shaft 1710. Such movement by the actuatable portion 1716 can beused, for example, to place the energy delivery element 1712 inapposition with a vessel wall at a treatment site, as explained ingreater detail below.

FIG. 17B is an enlarged side view of a portion of the distal portion1716, and FIG. 17C is a cross-sectional end view of the shaft 1710 takenalong line 17C-17C in FIG. 17B. Referring to FIGS. 17A-17C together, theactuatable portion 1716 can include four deflectable members 1714a-d(referred to collectively as deflectable members 1714) spaced apartabout the circumference of the shaft 1710. In the embodiment shown inFIGS. 17A-17C, the deflectable members 1714 are evenly spaced apartabout the circumference of the shaft 1710 such that each deflectablemember 1714 a-d corresponds to a distinct quadrant of the shaft 1710. Inother embodiments, the actuatable portion 1716 can include more or lessthan four deflectable members 1714 (e.g., one deflectable member, twodeflectable members, six deflectable members, etc.) and/or thedeflectable members 1714 can have any spacing about the shaft 1710. Eachof the deflectable members 1714 a-d can include a wire 1718 a-d,respectively, running therethrough (referred to collectively as wires1718). Each wire 1718 a-d can extend proximally from a proximal portionof one of the corresponding deflectable members 1714 a-d along the shaft1710 to the handle 1706. The wires 1718 can be electrically isolatedfrom one another in the shaft 1710 (e.g., via separate lumens (notshown), embedding the wires in a polymer, etc.). As such, each of thedeflectable members 1714 a-d can be independently electricallycontrolled from the handle assembly 1706.

In operation, upon positioning the distal portion 1704 of the shaft 1710at a treatment site adjacent a vessel wall (not shown), one or more ofthe deflectable members 1714 can be actuated to bend the distal portion1704 in a desired direction. For example, selection of deflectablemember 1714 a (e.g., via the control) sends a current distally along thewire 1718 a to the deflectable member 1714 a, thereby causing thedeflectable member 1714 a to bend outwardly (see arrow B_(a)) and awayfrom the longitudinal axis of the shaft 1710. The second-fourthdeflectable members 1714 b-d can be actuated in a similar fashion. Theability of the present technology to independently manipulate the distalportion of the shaft (relative to the rest of the shaft) can beadvantageous, especially in a pulmonary setting, to compensate for thepulsatile, dynamic flow conditions present with vessels in closeproximity to the heart. Moreover, such independent control can beadvantageous to finely tune the deformation of the distal portion toposition or navigate tortuous vasculature at and near the pulmonarysystem.

In some embodiments, the deflectable members 1714 a-d can individuallycomprise a bimetallic strip including a first material having a firstcoefficient of thermal expansion (CTE) positioned adjacent a secondmaterial having a second coefficient of thermal expansion (CTE) that isdifferent than the first CTE. The individual wires 1718 a-d can bepositioned between the corresponding first and second materials, and thefirst and second materials can be coupled to one another along theirlengths. As the current flows through the wire 1718, the first andsecond materials begin to heat. Because the first and second materialshave different CTE's, the lengths of the first and second materials willexpand at different rates. As a result, the deflectable member will bendin the direction of the material with the lower CTE. In someembodiments, the first and second materials can comprise platinum(linear CTE of about 9 (10⁻⁶ K⁻¹)), aluminum (CTE of about 22.2 (10⁻⁶K⁻¹)), silver (linear CTE of about 429 (10⁻⁶ K⁻¹)), and steel (linearCTE of about 13 (10⁻⁶ K⁻¹)).

Additionally, the deflectable members 1714 a-d can individually comprisea piezoelectric material (e.g., an electrical-mechanical polymer)positioned on or adjacent a substrate material. The piezoelectricmaterial and the substrate material can be coupled to one another alongtheir lengths such that, when current is applied to the deflectablemember (e.g., via the wire 1718), the piezoelectric material elongateswhile the substrate does not, thereby bending the deflectable member.

In some embodiments, the catheter 1700 can include a plurality ofactuatable portions spaced apart along the length of the shaft 1710.When actuated, the plurality of actuatable portions can bend the shaft1710 at multiple locations and/or in different directions. In suchembodiments, the number, size, shape and/or spacing of the deflectablemembers can be the same or different amongst the actuatable portions.

FIG. 18A is a perspective view of a portion of a catheter 1800 in alow-profile state configured in accordance with another embodiment ofthe present technology. As shown in FIG. 18A, the catheter 1800 caninclude a shaft 1810 having a proximal portion (not shown) and a distalportion configured to be intravascularly positioned at a treatment site.The distal portion can include a recessed portion 1816 and an atraumaticdistal end region 1812. The recessed portion 1816 can house a deformablemember 1802. An isolated, enlarged view of the deformable member 1802 isshown in FIG. 18B. Referring to FIGS. 18A and 18B together, thedeformable member 1802 can comprise a first conductive member 1806positioned on a second conductive member 1808. The first and secondmembers 1806, 1808 can individually comprise a metal. In someembodiments, the first member 1806 can be a first material having afirst CTE and the second member 1808 can be a second material having asecond CTE different than the first CTE. A wire 1814 extending from aproximal portion of the catheter 1800 (not shown) can be coupled to thefirst and second conductive members 1806, 1808. For example, the wire1814 can be positioned between the first and second members 1806, 1808.The first and second members 1806, 1808 can be coupled to one anotheralong their lengths. In some embodiments, the first and second memberscan individually comprise platinum (linear CTE of about 9 (10⁻⁶ K⁻¹)),aluminum (CTE of about 22.2 (10⁻⁶ K⁻¹)), silver (linear CTE of about 429(10⁻⁶ K⁻¹)), and steel (linear CTE of about 13 (10⁻⁶ K⁻¹)).

Referring still to FIGS. 18A-18B, the first and second conductivemembers 1806, 1808 can be coated or otherwise surrounded by aninsulative material. The first conductive member 1806 can include twoenergy delivery elements 1804 comprising an exposed portion of the firstconductive member 1806 (e.g., an opening in the insulative material). Inother embodiments, the deformable member 1804 can include more or lessthan two energy delivery elements (e.g., one energy delivery element,three energy delivery elements, etc.).

FIG. 18C is a side view of the distal portion of the catheter 1800 in alow-profile state, and FIG. 18D is a side view of the distal portion ofthe catheter 1800 in a deployed state. The sidewalls of the recessedportion 1816 are shown in phantom lines for ease of illustration.Referring to FIGS. 18A-18D together, as the current flows through thewire 1814, the first and second conductive members 1806, 1808 begin toheat. Because the first and second conductive members 1806, 1808 havedifferent CTE's, the lengths of the first and second conductive members1806, 1808 will expand at different rates. As a result, the deformablemember 1802 will bend in the direction of the material with the lowerCTE, thereby extending away from the longitudinal axis of the shaft 1810and into apposition with the vessel wall at the treatment site.

FIG. 19 is a schematic representation of a magnetically-deformablecatheter system 1900 configured in accordance with an embodiment of thepresent technology. As shown in FIG. 19, the catheter system 1900 caninclude a magnetic field generator 1902 (e.g., a magnetic resonanceimaging (MRI) system, etc.) configured to be positioned external to thepatient P and a catheter 1904. The catheter 1904 can include anelongated shaft 1910 and a magnetically actuatable portion 1906 coupledto a distal portion of the elongated shaft 1910. When the magnetic fieldgenerator 1902 is activated, the magnetic field deforms the magneticallyactuatable portion 1906 of the shaft 1910 (not shown) to achieve adesired shaft 1910 configuration.

The catheter 1904 of FIG. 19 can have only a single energy deliveryelement 1908 or, in other embodiments the catheter 1900 can include morethan one energy delivery element 1908 positioned along the shaft 1910.Additionally, the catheter 1900 can include more than one magneticallyactuatable portion 1906 positioned along the shaft 1910.

When modulating the nerves from within a pulmonary vessel, it isdesirable to avoid total occlusion of the vessel since 100% of thebody's blood flows through portions of the pulmonary vasculature (e.g.,the MPA). Several embodiments of the catheters, catheter systems, andmethods of the present technology provide non-occlusive means foreffectively modulating the nerves communicating with the pulmonarysystem. In other embodiments, the catheters, catheter systems, andmethods of the present technology can provide occlusive means foreffectively modulating nerves communicating with the pulmonary system.

FIGS. 20-21 are cross-sectional views of two additional embodiments ofsuch non-occlusive catheters. FIG. 20 shows a non-occlusive catheter2000 in a deployed state positioned in a vessel V and configured inaccordance with an embodiment of the present technology. As shown inFIG. 20, the catheter 2000 can include an ultrasound transducer 2002, afirst expandable member 2004 (e.g., a balloon, a wire cage, etc.)positioned around the ultrasound transducer 2002, and a secondexpandable member 2006 (e.g., a balloon, a wire cage, etc.) positionedadjacent the first expandable member 2004. When deployed, the first andsecond expandable members 2004, 2006 together position the ultrasoundtransducer 2002 near the vessel wall V at a desired distance to achieveeffective neuromodulation. As shown in FIG. 20, the diameters of thefirst and second expandable members 2004, 2006 can be selected such thatsufficient space S remains adjacent the catheter 2000 within the vesselV, thereby allowing blood flow during treatment.

FIG. 21 is a cross-sectional end view of another non-occlusive catheter2100 in a deployed state positioned in a vessel V and configured inaccordance with an embodiment of the present technology. As shown inFIG. 21, the catheter 2100 can include an ultrasound transducer 2102positioned within a donut-shaped expandable member 2104 (e.g., aballoon, a wire cage, etc.). During treatment, blood can flow throughthe opening in the expandable member 2104. It will be appreciated thatthe expandable members of the present technology can have any suitablesize, shape, and configuration. For example, in some embodiments, theexpandable members can have a helical/spiral shape in a deployed state.

E. Nerve Monitoring Devices and Methods

Any of the pulmonary neuromodulation systems and/or therapeuticassemblies described herein can be configured to stimulate nervesproximate the treatment site and/or record the resultant nerve activity.For example, several embodiments of the pulmonary neuromodulationsystems and/or therapeutic assemblies described herein can include anerve monitoring assembly. FIG. 22A, for example, is an enlargedisometric view of one embodiment of a nerve monitoring assembly 2300(also referred to herein as “monitoring assembly 2300”) configured inaccordance with the present technology. The monitoring assembly 2300 isconfigured to provide stimulation to neural fibers and/or recordactivity of nerves in communication with the pulmonary system. As shownin FIG. 22A, the monitoring assembly 2300 can include a first loopelectrode or conductor 2302 a and a second loop electrode or conductor2302 b (referred to collectively as loop electrodes 2302) electricallyisolated from the first loop electrode 2302 a and positioned at a distalportion 2312 of an elongated catheter shaft 2306. In the illustratedembodiment, the two loop electrodes 2302 form a generally circularshape. However, the term “loop electrode” as used herein should beconstrued broadly to include electrodes 2302 having other shapesconfigured to contact at least a portion of the interior wall of avessel. In various embodiments, the first loop electrode 2302 a can bean anode, the other loop electrode 2302 can be a cathode, and aninsulated portion 2304 can electrically isolate the anode and cathodeloop electrodes 2302 from one another and space the loop electrodes 2302laterally apart from one another. For example, the distal end of thefirst loop electrode 2302 a and the proximal end of the second loopelectrode 2302 b can terminate at or within a portion of the insulatingportion 2304, and the insulating portion 2304 can space apart the loopelectrodes 2302. In various embodiments, the separation between the loopelectrodes 2302 (e.g., provided by the insulating portion 2304) can beselected to enhance the signal to noise ratio for recording nerveactivity (e.g., delta fibers and/or C-fibers). For example, the firstand second loop electrodes 2302 a and 2302 b can be spaced about 5 mmapart from one another for recording action potentials from deltafibers, and may be positioned further apart from one another forrecording C-fibers.

When the first and second loop electrodes 2302 a and 2302 b areconfigured as an anode and a cathode, the monitoring assembly 2300 candeliver bipolar stimulation to nerves proximate a target site in avessel (e.g., nerves that communicate with the pulmonary system) orprovide bipolar recording of nerve activity proximate the target site.For example, a nerve monitoring device configured in accordance with oneembodiment of the present technology can include two electrodeassemblies 2300: a first electrode assembly configured to stimulatenerves and a second electrode assembly spaced apart from the firstelectrode assembly along the vasculature and configured to measure theaction potential of the nerves resulting from the stimuli of the firstelectrode assembly. Action potential is the electrical activitydeveloped in a nerve cell during activity (e.g., induced by a stimulusfrom the first electrode assembly).

The loop electrodes 2302 can have an outer diameter at least equal to aninner diameter of a target vessel and, in some cases, larger (e.g., 1.5times larger) than the inner diameter of the target vessel.

Each loop electrode 2302 can be made from a separate shape memory wirethat defines the electrode 2302. The shape memory wire allows the loopelectrodes 2302 to be positioned in a low profile, delivery state duringintravascular delivery to the target vessel and open transverse to thelongitudinal axis of the target vessel to an expanded or deployed state(shown in FIG. 22A). For example, the loop electrodes 2302 can be madefrom nitinol wires that can self-expand to a predefined shape upondelivery at the target vessel. In various embodiments, the shape memorymaterial can be coated (e.g., sputter coated) with gold, platinum,platinum iridium, and/or other suitable materials. The coating can beselected to substantially optimize the impedance of the assembly 2300and/or enhance the signal-to-noise ratio recorded by the electrodeassembly 2300. In other embodiments, the loop electrodes 2302 can bemade from other suitable materials (e.g., platinum, gold, platinumiridium, stainless steel, aluminum, etc.). The wire thickness of eachloop electrode 2302 can be sized such that the loop electrode 2302 isstable enough to maintain its shape during nerve monitoring, yetflexible enough to allow for intravascular delivery in a low profilearrangement to a peripheral vessel (e.g., a pulmonary blood vessel).

Each loop electrode 2302 of the monitoring assembly 2300 can have anexposed abluminal surface 2308 (e.g., an outer surface proximate thevessel wall during nerve monitoring) to deliver and/or receiveelectrical signals to neural fibers proximate to a target vessel and aninsulated adluminal or luminal surface 2310 (e.g., an inner surfacefacing away from the vessel wall and toward the lumen formed by thetarget vessel) to reduce the likelihood that blood flowing through thetarget vessel will short circuit the loop electrodes 2302. The luminalsurface 2310 may be insulated using a coating with a high dielectricconstant, strong adhesive properties to prevent it from rubbing offduring delivery, biocompatible properties suitable for intravascularuse, and/or other suitable characteristics.

As mentioned previously, the total exposed abluminal surface 2308 of themonitoring assembly 2300 can be selected to enhance the signal-to-noiseratio of the assembly 2300.

The monitoring assembly 2300 can be delivered intravascularly to atreatment site before and/or after neuromodulation. The distal portion2312 of the shaft 2306 can be made from various flexible polymericmaterials, such as a polyethylene block amide copolymer (e.g., PEBAX®,available from Arkema of France), high-density polyethylene (HDPE),nylon, polyimide, and/or other suitable materials, to facilitatenavigation through tortuous vasculature. The distal portion 2312 canalso include braid reinforcement comprised of polymeric materials toimprove column strength, torque, and reduce kinking. A proximal portion(not shown) of the shaft 2306 can be more stiff than the distal portion2312, and can therefore transmit force to track the shaft 2306 throughthe vasculature to the target site (e.g., proximate a pulmonary bloodvessel). The proximal portion 2313 can be made from PEBAX®, HDPE,low-density polyethylene (LDPE), nylon, polyimide, nylon, nitinol, astainless steel hypotube, and/or other suitable materials. In variousembodiments, the distal end portion of the assembly 2300 can include anatraumatic tip when the monitoring assembly 2300 is in the deliverystate to reduce trauma to vessel walls as the monitoring assembly 2300advances through the vasculature and deploys at the target site. Thisatraumatic tip material can be made from various soft materials, such asPEBAX®, LDPE, other polymers, and/or other suitable materials. Thedistal tip can also include a radiopaque tip marker (electricallyisolated from the loop electrodes 2302) to provide visualization of thedistal tip under fluoroscopy.

Signal wires 2311 (referred to individually as a first signal wire 2311a and a second signal wire 2311 b; shown in broken lines) can beoperatively coupled to the monitoring assembly 2300 to drive nervestimulation, record nerve activity, and/or otherwise provide a signal tothe loop electrodes 2302. The signal wires 2311, for example, can bewelded, soldered, crimped, and/or otherwise connected to the shaft 2306.A distal portion of the first signal wire 2311 a can be operably coupledto the first loop electrode 2302 a, and a distal portion of the secondsignal wire 2311 b can be operably coupled to the second loop electrode2302 b. The signal wires 2311 can extend through the shaft 2306 to aproximal end of the shaft where the signal wires 2311 can be operativelyconnected to a signal processing console (e.g., the energy generator 132of FIG. 1) suitable for nerve stimulation. In various embodiments, forexample, one or more electrode assemblies 2300 can be operativelycoupled to a NIM-Response Nerve Integrity Monitor (“NIM”) made availableby Medtronic Xomed of Jacksonville, Fla., which provides intraoperativenerve monitoring capabilities using visual and/or audible indications ofnerve activity. Additionally, in those embodiments where the catheterand/or treatment device includes an electrical element 211 (FIG. 2A),the signal wires 2311 can extend from the monitoring assembly 2300 tothe electrical element 211. In such embodiments, the catheter caninclude an additional set of wires (not shown) that extends between (andelectrically couples) the electrical element 211 and the energygenerator 132.

FIG. 22B is an enlarged partially schematic side view of a distalportion 2350 positioned in a blood vessel A (e.g., a pulmonary bloodvessel) and configured in accordance with an embodiment of the presenttechnology. The distal portion 2350 can include a therapeutic assembly2320 (shown schematically) and a nerve monitoring assembly 2330. Thetherapeutic assembly 2320 can include features generally similar to thefeatures of the therapeutic assemblies described above with reference toFIGS. 1-21. The nerve monitoring assembly 2330 can be generally similarto the nerve monitoring assembly 2300 of FIG. 22A. In the illustratedembodiment, the therapeutic assembly 2320 is operatively coupled to andpositioned between two electrode assemblies (identified individually asa first electrode assembly 2300 a and a second electrode assembly 2300b) which together define the nerve monitoring assembly 2330. In otherembodiments, the therapeutic assembly 2320 and the nerve monitoringassembly 2330 may be stand-alone devices that can be deliveredindependently to a target site (e.g., within the pulmonary artery). Forexample, in some embodiments the second electrode assembly 2300 b, thetherapeutic assembly 2320 and the first electrode assembly 2300 a arecoupled to separate catheter shafts and delivered sequentially to thetarget site to provide a configuration similar to that shown in FIG.22B. In still other embodiments, the first and second electrodeassemblies 2300 a and 2300 b can be integrally coupled to one anotherand delivered to the target site before and/or after neuromodulation.

The nerve monitoring assembly 2330 can be configured to stimulate nervesin communication with the pulmonary system proximally with the firstelectrode assembly 2300 a and record nerve activity distally with thesecond electrode assembly 2300 b. The second electrode assembly 2300 bcan be positioned distal to the first electrode assembly 2300 a. Infurther embodiments, the second electrode assembly 2300 b can beconfigured to provide stimulation and the first electrode assembly 2300a can be configured to record the resultant nerve activity.

The first and second electrode assemblies 2300 a and 2300 b can bespaced far enough apart from one another such that the signal artifactassociated with the bipolar stimulation from the first electrodeassembly 2300 a, which is less than that which would be produced bymonopolar stimulation, does not substantially engulf or otherwiseinterfere with the signal being recorded at the second electrodeassembly 2300 b. The magnitude of the signal artifact at the secondelectrode assembly 2300 b depends at least in part on the conductionvelocity of the nerve fibers and the spacing between the stimulus andrecording electrodes. C-fibers and delta-fibers, such as those found innerves, have relatively low conduction velocities (e.g., no more than 2m/s for C-fibers and about 3-13 m/s for delta fibers). As such, when thesecond electrode assembly 2300 b is configured to record activity ofnerves in communication with the pulmonary system, the second electrodeassembly 2300 b can be positioned laterally apart from the firstelectrode assembly 2300 a along the axis of the pulmonary vessel A toreduce the signal artifact recorded by the second electrode assembly2300 b. In further embodiments, at least one of the electrode assemblies2300 can be positioned outside the pulmonary blood vessel A. Forexample, in some embodiments the second electrode assembly 2300 b can bepositioned in the pulmonary blood vessel A to record nerve activity, andthe first electrode assembly 2300 a can be positioned elsewhere withinthe vasculature that can deliver a stimulus to nerves in communicationwith the pulmonary system. In still other embodiments, the firstelectrode assembly 2300 a can be configured to stimulate nerves from alocation outside the human body (e.g., at the brain stem), and thesecond electrode assembly 2300 b can be configured to record theresultant nerve activity at a site within or proximate to the pulmonaryblood vessel A. In additional embodiments, the electrode assemblies 2300can be configured to be placed at other suitable locations forstimulating and recording nerve activity.

In various embodiments, the first electrode assembly 2300 a can beconfigured to provide biphasic and bipolar stimulation. The second loopelectrode 2302 b ₁ (i.e., the electrode closest to the recording/secondelectrode assembly 2302 b) can be a cathode and the first loop electrode2302 a ₁ an anode. The second electrode assembly 2300 b can beconfigured to provide bipolar recording of nerve activity resulting fromthe stimulation induced by the first electrode assembly 2300 a. As such,the first loop electrode 2302 a ₂ can be one of an anode or a cathode,and the second loop electrode 2302 b ₂ can be the other of the anode orthe cathode. The second electrode assembly 2300 b can pick up therelatively small action potentials associated with activity of nerves incommunication with the pulmonary system, and can be sensitive torelatively small signals to differentiate nerve stimulation from noise.In order to pick up the small action potentials and differentiate thenerve activity from noise (e.g., from the signal artifact, actionpotentials of proximate muscle fibers, etc.), the second electrodeassembly 2300 b can be configured to record a plurality of samples thatcan be averaged (e.g., using an NIM or other suitable console). In oneembodiment, for example, the second electrode assembly 2300 b canaverage 160 samples within 12 seconds to identify the nerve activity. Inother embodiments, more or less samples can be averaged to identify thenerve activity.

As shown in FIG. 22B, the first and second electrode assemblies 2300 aand 2300 b and the therapeutic assembly 2320 can be attached to thedistal portion 2312 of the same shaft 2306 such that the nervemonitoring assembly 2330 and the therapeutic assembly 2320 can bedelivered as a unit to the target site. In one embodiment, for example,the therapeutic assembly 2320 includes a neuromodulation loop electrodethat is connected between the first and second electrode assemblies 2300a and 2300 b. The first and second electrode assemblies 2300 a and 2300b can be stiffer than the neuromodulation loop electrode such that theelectrode assemblies 2300 a-b stay substantially planar in the vessel Aand provide adequate contact with the arterial walls to stimulate thenerves and record the resultant nerve activity. The neuromodulation loopelectrode may be more flexible, allowing it to be pulled into a helix orcorkscrew configuration during deployment at the target site while thefirst and second electrode assemblies 2300 a and 2300 b stay anchoredagainst the vessel A due to self-expansion. In other embodiments, eachelectrode assembly 2300 a-b and/or the therapeutic assembly 2320 can beattached to separate shafts and delivered independently to the targetsite.

In various embodiments, the nerve monitoring assembly 2330 (inconjunction with or independent of the therapeutic assembly 2320) can bedelivered intravascularly to the pulmonary artery A or other peripheralvessel via a delivery sheath (not shown). The delivery sheath can extendalong the length of the shaft 2306, and can be made from PEBAX®, nylon,HDPE, LDPE, polyimide, and/or other suitable materials for navigatingthe vasculature. The delivery sheath can cover the electrode assemblies2300 a-b such that they are positioned in a low profile, delivery statesuitable for navigation through the vasculature. At the pulmonary vesselA, the delivery sheath can be moved relative to the electrode assemblies2300 a-b (e.g., the sheath can be retracted or the electrode assemblies2300 a-b can be advanced) to expose the electrode assemblies 2300 a-bfrom the sheath 2300. This allows the electrode assemblies 2300 a-b todeploy (e.g., self-expand) into an expanded state where the abluminalsurfaces 2308 of the loop electrodes 2302 contact the vessel wall. Inother embodiments, the delivery sheath is not integrated with the nervemonitoring assembly 2330, and is advanced over a guide wire to thetreatment site via a guide catheter. In this embodiment, the deliverysheath can be made from a soft, flexible material that allows it tonavigate tortuous vessels. Once the delivery sheath is at the targetsite in the pulmonary vessel A, the electrode assemblies 2300 a-b can bepositioned in a proximal opening of the delivery sheath and advanceddistally to the treatment site where they can be deployed to theexpanded state by moving the delivery sheath and the electrodeassemblies 2300 a-b relative to one another.

As shown in FIG. 22B, in the expanded state, the loop electrodes 2302 ofthe first and second electrode assemblies 2300 a and 2300 b are sized topress against or otherwise contact the interior wall of the pulmonaryvessel A. The nerve monitoring assembly 2330 can first monitor nerveactivity in real time before neuromodulation by delivering an electricalcurrent proximal to a treatment site via the first electrode assembly2300 a and recording the resultant nerve activity at the secondelectrode assembly 2300 b. The first and second loop electrodes 2302 a ₁and 2302 b ₁ of the first electrode assembly 2300 a can be operablycoupled to first and second signal wires 2311 a ₁ and 2311 b ₁,respectively, to provide bipolar stimulation, and the first and secondloop electrodes 2302 a ₂ and 2302 b ₂ of the second electrode assembly2300 b can be operably coupled to two separate signal wires 2311 a ₂ and2311 b ₂, respectively, to provide bipolar recording, or vice versa.Since the abluminal surface 2308 of the loop electrodes 2302 are fullyexposed, the first electrode assembly 2300 a can deliver stimulation tonerves positioned around the full circumference of the pulmonary vesselA. The exposed abluminal surface 2308 also allows the second electrodeassembly 2300 b to capture nerve activity regardless of nerveorientation around the circumference of the vessel A. The insulatedluminal surface 2310 of the loop electrodes 2302 insulates the electrodeassemblies 2300 from blood flowing through the pulmonary vessel A toavoid a short circuit between the electrode loops 2302. The recordingcan be visualized using a console (e.g., an NIM) coupled to the proximalportion (not shown) of the shaft 2306.

The therapeutic assembly 2320 can then apply an energy field to thetarget site to cause electrically-induced and/or thermally-inducedpartial or full denervation of the nerves in communication with thepulmonary system (e.g., using electrodes or cryotherapeutic devices).The nerve monitoring assembly 2330 can again stimulate and record thenerve activity to determine whether sufficient neuromodulation occurred.If the nerve monitoring assembly 2330 indicates the presence of a higherlevel of nerve activity than desired, the therapeutic assembly 2320 canagain apply the energy field to effectuate neuromodulation. This processof supplying a current, recording the resultant nerve activity, andapplying neuromodulation to the treatment site can be repeated until thedesired nerve lesion is achieved. In some embodiments, such as when thetherapeutic assembly 2320 uses cryotherapeutic cooling, the nervemonitoring assembly 2330 can also record nerve activity duringdenervation. Once nerve monitoring at the treatment site is complete,the delivery sheath can again be advanced over the electrode assemblies2300 a-b and/or the electrode assemblies 2300 a-b can be retracted intothe delivery sheath, thereby moving the electrode assemblies 2300 a-bback into the delivery state for removal from the patient.

In further embodiments, the nerve monitoring assembly 2330 can beoperatively coupled to the therapeutic assembly 2320 such that nervemonitoring and neuromodulation can run automatically as part of a presetprogram. In other embodiments, the nerve monitoring assembly 2330 is notpositioned around the therapeutic assembly 2320, but instead deliveredto the treatment site separately before and/or after neuromodulation bythe therapeutic assembly 2320.

In various embodiments, the first and second electrode assemblies 2300 aand 2300 b can be delivered after neuromodulation to confirm the desiredneuromodulation has occurred. For example, the two electrode assemblies2300 a-b can be delivered proximate the treatment site as separatecomponents or as an integrated unit to a vessel (e.g., the pulmonaryvessel) during the neuromodulation procedure a short time afterneuromodulation occurs (e.g., 5 minutes after neuromodulation). In otherembodiments, the electrode assemblies 2300 a-b can be used to monitornerve activity during a separate procedure following the neuromodulationprocedure (e.g., 1, 2 or 3 days after the neuromodulation procedure).

FIG. 23A is an enlarged isometric view of an electrode assembly 2400configured in accordance with another embodiment of the presenttechnology. The electrode assembly 2400 can include features generallysimilar to the assembly 2300 described above with reference to FIGS. 22Aand 22B. For example, the electrode assembly 2400 includes a loop 2402(e.g., a nitinol wire) at a distal portion 2412 of an elongated shaft2406 that is configured to provide bipolar, biphasic nerve stimulationand/or record the resultant nerve activity. However, the electrodeassembly 2400 shown in FIG. 23A includes a plurality of electrodes 2414(identified individually as first through sixth electrodes 2414 a-f,respectively) positioned around the circumference of the loop 2402spaced apart and electrically insulated from one another by insulatingsections 2416. The electrodes 2414 can be made from stainless steel,gold, platinum, platinum iridium, aluminum, nitinol, and/or othersuitable materials, and the insulation sections 2416 can be made from asuitable dielectric material (e.g., a high-k dielectric with strongadhesive properties). The electrodes 2414 can be substantially coplanarwith an outer surface of the insulating sections 2416 and/or the shaft2406, or may project beyond the insulating sections 2416 by a distance.In various embodiments, for example, the electrodes 2414 can extend aradial distance from the adjacent insulating portions 2416 and include asmoothed edge (e.g., a beveled edge) to reduce denuding of the adjacentarterial wall. The coplanar or projecting electrodes 2414 can facilitatecontact with the arterial wall to enhance stimulation and/or recording.In other embodiments, one or more of the electrodes 2414 may be recessedfrom the insulating portions 416.

In the illustrated embodiment, the multi-electrode loop 2402 includessix electrodes 2414 a-f, which may be suitable for loops having outerdiameters of approximately 8 mm. In other embodiments, however, the loop2402 can include more or less electrodes 2414 (e.g., four to eightelectrodes 2414) depending at least in part on the outer diameter of theloop 2402. Each of the electrodes 2414 can be designated as a cathode,anode, or inactive by a nerve monitoring console (e.g., an NIM and/orother suitable console) operably coupled to the multi-electrode loop2402 via signal wires extending through the shaft 2406. For example, theelectrodes 2414 can alternate as anodes and cathodes around thecircumference of the loop 2402 (e.g., the first, third and fifthelectrodes 2414 a, 2414 c and 2414 e can be anodes and the second,fourth and sixth electrodes 2414 b, 2414 d and 2414 f can be cathodes)such that the single loop 2402 can provide bipolar stimulation orrecording. Similar to the loop electrodes 2302 described above, aluminal surface 2410 of the multi-electrode loop 2402 can also beinsulated to inhibit short circuits across the electrodes 2414 (e.g.,via blood or other conductive pathways), while an abluminal surface 2408can remain exposed to allow the electrodes 2414 to contact a vessel wall(e.g., the pulmonary blood vessel).

In various embodiments, the electrode assembly 2400 can include twoloops 2402 spaced laterally apart from one another (e.g., similar to thedual loop electrode assembly 2300 shown in FIG. 22A). This arrangementallows all the electrodes 2414 on one multi-electrode loop 2402 to beconfigured as anodes, while all the electrodes 2414 on the othermulti-electrode loop 2402 can be configured as cathodes. Much like theloop electrodes 2302 shown in FIG. 22A, the double multi-electrode loopconfiguration can increase the surface area with which the electrodeassembly 2400 can stimulate and/or capture nerve activity, and cantherefore enhance nerve monitoring.

FIG. 23B is an enlarged partially schematic side view of a distalportion of a treatment device 2450B within a blood vessel A (e.g., apulmonary vessel) configured in accordance with another embodiment ofthe present technology. The treatment device 2450B includes featuresgenerally similar to the features of the treatment device 2350 describedabove with reference to FIG. 22B. For example, the treatment device2450B includes a therapeutic assembly 2420 positioned between andoptionally operably coupled to a first electrode assembly 2400 a and asecond electrode assembly 2400 b. The first electrode assembly 2400 aincludes two multi-electrode loops 2402 (identified individually as afirst multi-electrode loop 2402 a and a second multi-electrode loop 2402b). In various embodiments, all the electrodes 2414 of the firstmulti-electrode loop 2402 a can be anodes, and all the electrodes 2414of the second multi-electrode loop 2402 b can be cathodes such that thefirst electrode assembly 2400 a can provide bipolar nerve stimulation.In the embodiment illustrated in FIG. 23B, the second electrode assembly2400 b includes one multi-electrode loop 2402 having both anodes andcathodes spaced around the circumference to provide bipolar recording ofnerve activity. In other embodiments, the second electrode assembly 2400b can include two multi-electrode loops 2402 and designate one as acathode and the other as an anode. In further embodiments, the firstelectrode assembly 2400 a and/or the second electrode assembly 2400 bcan include two bare loop electrodes 2302 as shown in FIG. 22B. In stillfurther embodiments, the electrode assemblies 2400 can be configured toprovide monopolar nerve stimulation or recording.

FIG. 23C is an enlarged partially schematic side view of a distalportion of a treatment device 2450C within a blood vessel A (e.g., apulmonary blood vessel) in accordance with yet another embodiment of thepresent technology. The treatment device 2450C includes featuresgenerally similar to the features of the treatment device 2450Bdescribed above with reference to FIG. 22B. For example, the treatmentdevice 2450C includes the therapeutic assembly 2420 positioned betweenthe first electrode assembly 2400 a and the second electrode assembly2400 b. In the embodiment illustrated in FIG. 23C, however, the firstelectrode assembly 2400 a includes only one multi-electrode loop 2402such that the loop 2402 includes both anodes and cathodes to provide thedesired bipolar stimulation.

FIG. 24 is an enlarged partially schematic side view of a distal portionof a treatment device 2550 within a blood vessel A (e.g., a pulmonaryblood vessel) in accordance with a further embodiment of the presenttechnology. The treatment device 2550 includes features generallysimilar to the features of the treatment devices described above withreference to FIGS. 22B, 23B and 23C. The treatment device 2550, forexample, includes a therapeutic assembly 2520 (shown schematically) anda nerve monitoring assembly 2530 at a distal portion 2512 of a shaft2506. The therapeutic assembly 2520 is positioned between a firstelectrode assembly 2500 a that provides bipolar nerve stimulation and asecond electrode 2500 b that provides bipolar recording of nerveactivity (collectively referred to as electrode assemblies 2500). In theillustrated embodiment, each electrode assembly 2500 includes a balloon2532 (identified individually as a first balloon 2532 a and a secondballoon 2532 b) having one or more conductive portions 2534 (identifiedindividually as a first conductive portion 2534 a and a secondconductive portion 2534 b) that serve as electrodes. The conductiveportions 2534 can be made from a conductive ink that is sufficientlyflexible to allow the balloons 2532 to fold into a guide catheter (notshown) during delivery and removal of the treatment device 2550. Inother embodiments, the conductive portions 2534 can be made from othersuitable materials that attach to the balloons 2532, such as platinumiridium wires.

In the embodiment illustrated in FIG. 24, each balloon 2532 includes twospaced apart conductive portions 2534 around at least a portion of thecircumference of the balloon 2532 such that the conductive portions 2534can contact the inner wall of the blood vessel A when the balloons 2532are inflated (e.g., as shown in FIG. 24). The balloons 2532 can beinflated by flowing gas (e.g., air) or liquid (e.g., saline solution)into the balloons 2532 through one or more openings 2537 (referred toindividually as a first opening 2537 a and a second opening 2537 b) in atube 2535 that is coupled to a fluid source (not shown) at a proximalend portion and extends through the balloons 2532 at a distal endportion. Similar to the multi-loop electrode assemblies described above,the two conductive portions 2534 of each balloon 2532 can be designatedas an anode and as a cathode to provide bipolar nerve stimulation andrecording. In other embodiments, at least one of the electrodeassemblies 2500 can include a dual balloon, and each balloon can includeone conductive portion 2534 such that the nerve monitoring assembly 2530includes three or four balloons.

In various embodiments, the therapeutic assembly 2520 can be omitted. Assuch, the electrode assemblies 2500 can be intravascularly delivered tothe treatment site (e.g., at the pulmonary vessel) to record nerveactivity before neuromodulation. The electrode assemblies 2500 can thenbe removed from the target site to allow the therapeutic assembly 2520to be delivered. After neuromodulation, the electrode assemblies 2500can be delivered back to the target site to record the nerve activity.If a sufficient nerve lesion has not been formed, the therapeuticassembly 2520 can again be delivered to the treatment site to deliver anenergy field to ablate or otherwise modulate the nerves. The therapeuticassembly 2520 can then be removed from the treatment site to allow theelectrode assemblies 2500 to be delivered and monitor the resultantnerve activity. This process can be repeated until a sufficient nervelesion is formed at the target site.

FIG. 25 is an enlarged side view of a distal portion of a treatmentdevice 2650 within a blood vessel A (e.g., a pulmonary blood vessel) inaccordance with yet another embodiment of the present technology. Thetreatment device 2650 includes a number of features generally similar tothe features of the treatment devices described above with reference toFIGS. 22B, 23B, 23C and 24. For example, the treatment device 2650includes an array of electrodes (identified individually as a firstelectrode array 2600 a and a second electrode array 2600 b, and referredto collectively as electrode arrays 2600) proximal and distal to aneuromodulation area 2643 (shown in broken lines). In the embodimentillustrated in FIG. 25, the treatment device 2650 has a double balloonconfiguration in which a first inflatable body or outer balloon 2640 isdisposed over a second inflatable body or inner balloon 2642. The innerballoon 2642 can be configured to deliver therapeutic neuromodulation tonerves proximate a treatment site (e.g., a pulmonary blood vessel). Forexample, the inner balloon 2642 can define an expansion chamber in whicha cryogenic agent (e.g., nitrous oxide (N₂O)) can expand to providetherapeutically-effective cooling to tissue adjacent to the inflatedinner balloon 2642 (e.g., in the neuromodulation area 2643). In otherembodiments, the inner balloon 2642 can be configured to providetherapeutic neuromodulation using other suitable means known in the artsuch as ultrasound (e.g., HIFU). In further embodiments, the innerballoon 2642 may be omitted, and energy deliver elements (e.g.,electrodes) can be disposed on an outer surface of the outer balloon2640 to deliver RF ablation energy and/or other forms of energy forneuromodulation.

As shown in FIG. 25, a proximal end portion of the outer balloon 2640can be coupled to a distal portion 2612 of an outer shaft 2606 and aproximal end portion of the inner balloon 2642 can be coupled to aninner shaft 2644 that extends through the outer shaft 2606. In theillustrated embodiment, the inner shaft 2644 extends through the outerand inner balloons 2640 and 2642 such that the distal end portions ofthe outer and inner balloons 2640 and 2642 can connect thereto, andtherefore the inner shaft 2644 can provide longitudinal support alongthe balloons 2640 and 2642. In other embodiments, the inner shaft 2644can extend partially into the balloons 2640 and 2642 or terminateproximate to the distal end of the outer shaft 2606. The outer and innershafts 2606 and 2644 can define or include supply lumens fluidly coupledat proximal end portions to one or more fluid sources and fluidlycoupled at distal end portions to the outer and inner balloons 2640 and2642. For example, the inner shaft 2644 can include one or more openings2646 through which fluids (e.g., refrigerants or other cryogenic agents)can be delivered to the inner balloon 2642 (e.g., as indicated by thearrows) to inflate or expand the inner balloon 2642. Fluids (e.g.,saline or air) can be delivered to the outer balloon 2640 through aspace or opening 2646 between the outer and inner shafts 2606 and 2644(e.g., as indicated by the arrows) and/or by a supply lumen spacedtherebetween to inflate or expand the outer balloon 2640.

The inner balloon 2642 can have smaller dimensions than the outerballoon 2640 such that the outer balloon 2640 expands into fullcircumferential contact with the vessel wall along a length of thevessel and the inner balloon 2642 expands to press against or otherwisecontact a segment of the inner wall of the outer balloon 2640. In theembodiment illustrated in FIG. 25, for example, the outer and innerballoons 2640 and 2642 contact each other at an interface extendingaround a full circumference of the inner balloon 2642 spaced laterallyinward of the electrode arrays 2600. The portion of the outer balloon2640 in contact with the inflated inner balloon 2642 can delivertherapeutically-effective neuromodulation (e.g., via cryotherapeuticcooling) to nerves proximate the adjacent vessel wall. Accordingly, thedouble balloon arrangement shown in FIG. 25 can deliverfully-circumferential neuromodulation. Non-targeted tissue proximal anddistal to the contacting balloon walls is shielded or protected fromneuromodulation by an inflation medium (e.g., saline solution, air,etc.) within the outer balloon 2640, which may effectively act asinsulation.

The outer and inner balloons 2640 and 2642 can be made from variouscompliant, non-compliant, and semi-compliant balloons materials. Theouter balloon 640, for example, can be made from a compliant balloonmaterial (e.g., polyurethane or silicone) such that when the outerballoon 2640 is inflated, it can press against the inner wall of avessel to provide stable contact therebetween. The inner balloon 2642can be made from semi-compliant and or non-compliant materials (e.g.,formed from polyether block amide, nylon, etc.) to define a smallerexpanded size. In other embodiments, the outer and inner balloons 2640and 2642 can be made from other suitable balloon materials.

As shown in FIG. 25, the first electrode array 2600 a and the secondelectrode array 2600 b may be located at the outer wall of the outerballoon 2640 and positioned proximal and distal to the neuromodulationarea 2643 (i.e., the region of the outer balloon 2640 that contacts theinflated inner balloon 2642). Each electrode array 2600 can include afirst conductive portion 2634 a and a second conductive portion 2634 b(referred to collectively as conductive portions 2634) that extendaround the circumference of the outer balloon 2640 to define first andsecond electrode loops. In other embodiments, one or both of theelectrode arrays 2600 can include a single conductive portion or stripextending around the circumference of the outer balloon 2640. Theconductive portions 2634 can be made from a conductive ink printed onthe outer wall of the outer balloon 2640 and/or other conductivematerials that can attach to the outer balloon 2640. In operation, thefirst electrode array 2600 a can stimulate nerves proximal to theneuromodulation area 2643 and the second electrode array 2600 b cansense the resultant stimulation, or vice versa. The first and secondconductive portions 2634 of each electrode array 2600 can be configuredto provide bipolar or monopolar stimulation and/or recording dependingupon which mode provides the highest signal response. For example, thefirst electrode array 2600 a can include one electrode (e.g., oneconductive strip 2634) for monopolar stimulation and the secondelectrode array 2600 b can include two electrodes (e.g., two conductivestrips 2634) for bipolar recording. In other embodiments, however, theelectrode arrays 2600 may have other arrangements and/or includedifferent features.

The treatment device 2650 can provide nerve stimulation and recordingbefore, during, and/or after neuromodulation. For example, the electrodeassemblies 2600 can stimulate nerves and record the resultant nerveactivity before neuromodulation to provide a set point against whichsubsequent nerve monitoring can be compared. This information can alsobe used to determine the level of power or current that must bedelivered to ablate the nerves since each patient typically hasdifferent base line levels nerve activity. Therefore, the electrodearrays 2600 can also provide diagnostic nerve monitoring. During theneuromodulation procedure, the electrode arrays 2600 can monitor thereduction of nerve signal strength to confirm the effectiveness of theneuromodulation. For example, the electrode assemblies 2600 cancontinually monitor nerve activity during neuromodulation byinterleaving stimulation pulses and recording periods. In otherembodiments, nerve monitoring periods can be spaced betweenneuromodulation periods to determine whether the nerves have beensufficiently modulated or if subsequent neuromodulation cycles arenecessary to provide the desired modulation.

FIG. 26 is an enlarged side view of a distal portion of a treatmentdevice 2750 within a blood vessel A (e.g., a pulmonary blood vessel) inaccordance with a further embodiment of the present technology. Thetreatment device 2750 includes a number of features generally similar tothe features of the treatment device 2650 described above with referenceto FIG. 25. For example, the treatment device 2750 includes an outerballoon 2740 in fluid communication with a first supply lumen via anopening 2746 at a distal portion 2712 of an outer shaft 2706, and aninner balloon 2742 in fluid communication with a second supply lumen viaan opening 2746 of an inner shaft 2744. The outer balloon 2740 can beinflated with a non-therapeutically effective fluid (e.g., air) to pressagainst and maintain contact with the inner vessel wall. The innerballoon 2742 can be inflated with a cryogenic agent (e.g., arefrigerant) and/or other fluid to contact a portion of the outerballoon 2740 and provide neuromodulation (e.g., via cryotherapeuticcooling or ultrasound) about the full circumference of an adjacentvessel wall (e.g., within a neuromodulation region 2743).

The treatment device 2750 also includes first and second electrodearrays 2700 a and 2700 b (referred to collectively as electrode arrays2700) proximal and distal to the portion at which the inner balloon 2742contacts the outer balloon 2740. Rather than continuous conductivestrips around the circumference of the outer balloon 2740, however, theelectrode arrays 2700 illustrated in FIG. 26 include a plurality ofpoint electrodes 2748 on or in an outer wall of the outer balloon 2740.The point electrodes 2748, for example, can be made from conductive inkprinted on the outer balloon 2740, conductive pads adhered to the outerballoon 2740, and/or other suitable conductive features. The individualpoint electrodes 2748 can be oriented about the circumference of theouter balloon 2740 in various different patterns and provide monopolarand/or bipolar nerve stimulation and recording before, during and/orafter neuromodulation.

FIG. 27 is an enlarged side view of a distal portion of a treatmentdevice 2850 within a blood vessel A (e.g., a pulmonary blood vessel) inaccordance with an additional embodiment of the present technology. Thetreatment device 2850 includes several features generally similar to thefeatures of the treatment device 2650 described above with reference toFIG. 25. For example, the treatment device 2850 includes first andsecond electrode arrays 2800 a and 2800 b (referred to collectively aselectrode arrays 2800) on an outer balloon 2840 and positioned proximaland distal to a neuromodulation region 2843 provided by an inner balloon2842. In the embodiment illustrated in FIG. 27, the inner balloon 2842has a smaller outer diameter in an inflated state than that of the outerballoon 2840 and is attached to an interior surface of the outer balloon2840 using an adhesive, a heat-bond and/or other types of balloonconnection. The outer balloon 2840 can be fluidly coupled to a supplylumen defined by a shaft 2844 that delivers an insulative medium (e.g.,a heated liquid, heated gas, ambient air, etc.) to the outer balloon2840 via openings 2846, and the inner balloon 2842 can be fluidlycoupled to a separate supply lumen (not shown) that delivers aninflation fluid (e.g., a cryogenic agent) to the inner balloon 2842.

In use, the outer balloon 2840 expands into full circumferential contactwith the vessel wall to provide tissue apposition for signal transfer toand from the vessel wall via the electrode arrays 2800. The innerballoon 2842 is essentially radially pulled toward only the portion ofthe vessel wall adjacent to where the inner balloon 2842 is attached tothe outer balloon 2840. When a cryogenic agent and/or other therapeuticmedium is introduced into the inner balloon 2842, non-targeted tissuethat is not adjacent to the inner balloon 2842 is shielded or protectedfrom ablation by the inflation medium located within the outer balloon2840. The targeted tissue adjacent to the inner balloon 2842 is ablated,resulting in a partial circumferential neuromodulation. The innerballoon 2842 can be shaped or otherwise configured to provide anon-continuous, helical, and/or other type of ablation pattern.

FIG. 28 is a block diagram illustrating a method 2900A of endovascularlymonitoring nerve activity in accordance with an embodiment of thepresent technology. The method 2900A can include deploying a nervemonitoring assembly and a therapeutic assembly in a vessel (e.g., apulmonary blood vessel; block 2902). The nerve monitoring assembly caninclude a plurality of multi-electrode rings (e.g., similar to themulti-electrode loops 2402 described above with reference to FIGS.23A-23C) connected to a distal portion of a catheter shaft. Themulti-electrode rings can be made of nitinol or other shape memorymaterials such that they can be deployed by simply moving the cathetershaft and a sheath covering the multi-electrode rings relative to oneanother (e.g., pulling the sheath proximally, pushing the catheter shaftdistally, etc.). Each multi-electrode ring can include a plurality ofelectrodes spaced around the circumference of the ring andcommunicatively coupled to signal wires extending through the cathetershaft. The signal wires can extend outside the body where they areoperably coupled to a signal generator and/or receiver (e.g., an NIM) togenerate stimuli and record the resultant action potential of theproximate neural fibers.

When the therapeutic assembly is deployed, at least one and often two ormore multi-electrode rings (“distal rings”) or another distal electrodeassembly can be positioned distal to the therapeutic assembly and atleast one multi-electrode ring (“proximal ring”) or other proximalelectrode assembly can be positioned proximal to the therapeuticassembly. In other embodiments, the nerve monitoring assembly caninclude one, two, or more multi-electrode rings on either side of thetherapeutic assembly. In further embodiments, other types of electrodearrays can be positioned proximal and distal to the therapeuticassembly. The therapeutic assembly, such as a single- or multi-electrodedevice or a cryoballoon, can be integrated with the same catheter shaftas the multi-electrode rings and positioned between the proximal anddistal rings. In other embodiments, the therapeutic assembly can beattached to a separate catheter shaft and deployed between proximal anddistal multi-electrode rings.

The method 2900A can further include delivering a plurality of short,high current stimulus pulses through the electrodes on one or both ofthe multi-electrode rings positioned distal to the therapeutic assembly(block 2904), and analyzing an electrogram of at least one of theelectrodes on the proximal ring resulting from the stimulus pulse (block2906). For example, a signal generator can pass a current having amagnitude of about 10-60 mA (e.g., 20 mA, 50 mA, etc.) for a pulselength of about 25-1,500 μs (e.g., 100-400 μs, 1 ms, etc.) between theelectrodes of the distal rings in the delivering process 2904. Thesignal generator can also control the frequency of the signal such thatthe signal has a frequency of about 10-50 Hz (e.g., 20 Hz). After apredetermined time interval, a separate electrogram can be recordedthrough at least one electrode on the proximal ring. For example, aseparate electrogram can be recorded through each of the electrodes ofthe proximal electrode ring. The length of the time interval betweenstimulation and recording depends on the separation of the distal andproximal rings along the length of the vessel such that the proximalring picks up the signal resulting from the induced stimulus. Forexample, the time interval can be about 10-50 ms for rings spaced 10-50mm apart. In an alternative embodiment, the delivering process (block2904) of the method 2900A can include delivering the short, high currentstimulus pulses through at least one of the proximal electrode rings(e.g., proximal electrode assembly), and the analyzing process (block2906) of the method 2900A can include analyzing an electrogram of atleast one of the electrodes of the distal electrode rings (e.g., distalelectrode assembly).

The method 2900A can further include providing therapeutically-effectiveneuromodulation energy (e.g., cryogenic cooling, RF energy, ultrasoundenergy, etc.) to a target site using the therapeutic assembly (block2908). After providing the therapeutically-effective neuromodulationenergy (block 2908), the method 2900A includes determining whether theneuromodulation therapeutically treated or otherwise sufficientlymodulated nerves or other neural structures proximate the treatment site(block 2910). For example, the process of determining whether theneuromodulation therapeutically treated the nerves can includedetermining whether nerves were sufficiently denervated or otherwisedisrupted to reduce, suppress, inhibit, block or otherwise affect theafferent and/or efferent pulmonary signals.

FIG. 29 is a block diagram illustrating a method 2900B of endovascularlymonitoring nerve activity in accordance with an embodiment of thepresent technology. The method 2900B can include deploying a nervemonitoring assembly and a therapeutic assembly in a vessel (block 2902)and delivering short, high current signal pulses through an electrodeassembly (block 2904) as described above with respect to the method2900A in FIG. 28. In this embodiment, the analyzing process (block 2906of FIG. 28) can optionally include recording the electrograms for eachelectrode on the proximal electrode ring or other proximal electrodeassembly (block 2906-1) and signal averaging a plurality of the recordedelectrode signals (e.g., 10-100 recorded electrode signals) resultingfrom a corresponding plurality of stimulus pulses to enhance therecorded signal (block 2906-2).

The method 2900B can optionally include identifying the nerve locationproximate one or more of the electrode rings. For example, one or moreof the recorded electrode signals may include a deflection or otherchange in the recorded current indicating an action potential caused bythe stimulus (e.g., identified via signal averaging) indicating thetransmission of an electrical impulse from the stimulus pulse viaadjacent nerves. Electrode signals that include changes in currentintensity correspond with the electrodes on the proximal ring positionedproximate to nerves. The higher the deflection or change in currentintensity, the closer the electrode is to the nerves. This informationcan be used to identify electrodes on the proximal ring close to thenerves for effective nerve stimulation or recording (block 2907-1).Optionally, the method 2900 can include stimulating nerves via theproximal ring and recording electrograms of the individual electrodes atone of the distal rings to determine the location of nerves proximatethe distal rings (block 2907-2).

The method 2900B can also include providing therapeutically-effectiveneuromodulation energy (e.g., cryogenic cooling, RF energy, ultrasoundenergy, etc.) to a target site using the therapeutic assembly (block2908). In this embodiment, the process of determining whether theneuromodulation treated the nerves proximate the target site (block 2910in FIG. 28) can include repeating the nerve stimulation (block 2904) andanalyzing processes (block 2906) discussed above to assess whether theneuromodulation caused any changes in the nerve activity (block 2910-1).For example, short, high current stimulus pulses can be transmitted viathe proximal or distal rings and the resultant nerve activity can berecorded by the opposing ring(s). The method 2900B can then determinewhether the nerves have been adequately modulated (block 2912). Forexample, if the current density or other parameter observed in therecording electrodes proximate the nerve locations is below a thresholdvalue, then the neuromodulation step may have effectively modulated orstopped conduction of the adjacent nerves and the neuromodulationprocess can be complete. On the other hand, if nerve activity isdetected above a threshold value, the process of neuromodulating (block2908) and monitoring the resultant nerve activity (block 2910-1) can berepeated until the nerves have been effectively modulated.

In various embodiments, the methods 2900A and 2900B can also includerepeating the nerve monitoring and neuromodulation steps in the oppositedirection to confirm that the nerves have been adequately modulated. Themethods 2900A and 2900B can also optionally be repeated after a timeperiod (e.g., 5-30 minutes, 2 hours, 1 day, etc.) to confirm that thenerves were adequately ablated (e.g., rather than merely stunned) andhave not resumed conduction.

In other embodiments, the methods 2900A and 2900B can be performed usingother nerve monitoring assemblies or electrode arrays described abovewith reference to FIGS. 22A-29 and/or other suitable electrodearrangements. For example, the therapeutic assembly can include multiplepoint electrodes spaced around the circumference of a balloon asdescribed above with respect to FIG. 27. In other embodiments,continuous wire loop electrodes and/or conductive strips on balloons canbe used to identify nerve location and monitor nerve activity.

III. Examples

1. A catheter apparatus, comprising:

-   -   an elongated shaft having a proximal portion and a distal        portion, wherein the distal portion of the shaft is configured        for intravascular delivery to a body vessel of a human patient;    -   an energy delivery element positioned along the distal portion        of the shaft; and    -   a plurality of deflectable members spaced apart about a        circumference of the distal portion of the shaft, wherein each        of the deflectable members is configured to transform from a        low-profile state to a deployed state, thereby bending the        distal portion and placing the energy delivery element in        apposition with a wall of the body vessel.

2. The catheter apparatus of example 1 wherein the distal portion of theelongated shaft is sized and configured for intravascular delivery intothe pulmonary artery.

3. The catheter apparatus of example 1 or example 2 wherein the each ofthe deflectable members comprises a bimetallic strip including a firstmaterial having a first coefficient of thermal expansion (CTE)positioned adjacent a second material having a second CTE that isdifferent than the first CTE.

4. The catheter apparatus of any of examples 1-3 wherein each of thedeflectable members comprises a bimetallic strip including apiezoelectric material and a substrate material coupled to one anotheralong their lengths, wherein the piezoelectric material has a first CTEand the substrate material has a second CTE that is different than thefirst CTE.

5. The catheter apparatus of any of examples 1-4 wherein the therapeuticassembly comprises four deflectable members, wherein each of thedeflectable members corresponds to a distinct quadrant of the shaft.

6. The catheter apparatus of any of examples 1-5 wherein the deflectablemembers extend along a length of the shaft and have a proximal terminuswithin the distal portion of the elongated shaft.

7. The catheter apparatus of any of examples 1-6 wherein the deflectablemembers have a length less than a length of the elongated shaft and aproximal terminus spaced distally apart from a proximal portion of theshaft.

8. The catheter apparatus of any of examples 1-7 wherein the deflectablemembers have distal terminus spaced proximally of the energy deliverydevice and a proximal terminus within the distal portion of theelongated shaft.

9. The catheter apparatus of any of examples 1-8 wherein the energydelivery element is a single energy delivery element positioned at adistal terminus of the shaft.

10. The catheter apparatus of any of examples 1 and 3-10 wherein thedistal portion of the elongated shaft is sized and configured forintravascular delivery into the renal artery.

11. The catheter apparatus of any of examples 1-10, further comprising ahandle at the proximal portion of the shaft, the handle including anactuator that is electrically coupled to each of the deflectablemembers, and wherein the deflectable members are independentlytransformable between their respective low-profile states and deployedstates by activating the actuator.

12. The catheter apparatus of any of examples 1-11 wherein the energydelivery element is spaced apart from the deflectable members along theshaft.

13. The catheter apparatus of any of examples 1-11 wherein the energydelivery element is positioned on one or more of the deflectablemembers.

14. The catheter apparatus of any of examples 1-13 wherein the energydelivery element is a first energy delivery element, and wherein thecatheter apparatus further comprises a second delivery element.

15. A catheter apparatus, comprising:

-   -   an elongated shaft having a proximal portion and a distal        portion, wherein the distal portion of the shaft is configured        for intravascular delivery to a body vessel of a human patient;    -   a deflectable member at the distal portion of the shaft and        electrically coupled to the proximal portion, wherein the        deflectable member comprises a bimetallic strip including a        first material having a first CTE positioned adjacent a second        material having a second CTE that is different than the first        CTE; and    -   an energy delivery element on the deflectable member,    -   wherein heating the deflectable member deforms the deflectable        member, thereby placing the energy delivery element in        apposition with a wall of the body vessel.

16. The catheter apparatus of example 15 wherein the energy deliveryelement is a first energy delivery element, and wherein the catheterapparatus further comprises a second delivery element on the deflectablemember.

17. The catheter apparatus of example 15 or example 16 wherein theenergy delivery element is in direct contact with the deflectablemember.

18. The catheter apparatus of any of examples 15-17 wherein thedeflectable element is a first deflectable element, and wherein thecatheter apparatus further comprises a second deflectable element.

19. A method, comprising:

-   -   intravascularly positioning a therapeutic assembly at a        treatment site within a blood vessel, wherein the therapeutic        assembly includes a deflectable member and an energy delivery        element;    -   heating the deflectable member to position the energy delivery        element in apposition with the blood vessel wall; and    -   ablating nerves proximate the treatment site via the energy        delivery element.

20. The method of example 19 wherein intravascularly positioning thetherapeutic assembly includes intravascularly positioning thetherapeutic assembly within a pulmonary blood vessel.

21. The method of example 19 wherein intravascularly positioning thetherapeutic assembly includes intravascularly positioning thetherapeutic assembly within a renal blood vessel.

22. A treatment device, comprising:

-   -   a shaft including a proximal portion and a distal portion,        wherein the shaft is configured to intravascularly locate the        distal portion at a treatment site within a pulmonary blood        vessel of a human patient;    -   a balloon at the distal portion of the shaft;    -   a lumen extending distally from a proximal portion of the shaft        to an output port at the distal portion, wherein the output port        is positioned along a portion of the shaft within the balloon,        and wherein the output port is configured to deliver a cooling        agent to an interior portion of the balloon;    -   a first electrode positioned on the outer surface of the balloon        and extending about at least a portion of the circumference of        the balloon;    -   a second electrode positioned on the outer surface of the        balloon and extending about at least a portion of the        circumference of the balloon, wherein the first electrode is        spaced apart from and out of contact with the second electrode        along the balloon;    -   wherein the first and second electrodes are configured to—        -   deliver therapeutic neuromodulation to nerves in            communication with the pulmonary system proximate the            treatment site, and        -   stimulate nerves and/or record nerve activity at the            treatment site.

23. The treatment device of example 22 wherein the first electrode isconfigured to stimulate nerves proximate the treatment site and thesecond electrode is configured to record nerve activity at the treatmentsite during and/or after the therapeutic neuromodulation.

24. The treatment device of example 22 or example 23, further comprisingan insulated portion between the first electrode and the secondelectrode on the outer surface of the balloon.

25. The treatment device of any of examples 22-24 wherein:

-   -   the first electrode is configured to deliver energy sufficient        to modulate the nerves in communication with the pulmonary        system; and    -   the second electrode is configured for bipolar recording of the        nerve activity before, during, and/or after energy application.

26. The treatment device of any of examples 22-25 wherein the lumen is afirst lumen, and wherein the shaft further includes a second lumenextending distally to an inlet port positioned along a portion of theshaft within the balloon.

27. The treatment device of any of examples 22-26 wherein at least oneof the first and second electrodes includes a multi-electrode loophaving at least two electrodes spaced circumferentially about the loop.

28. The treatment device of any of examples 22-27 wherein at least oneof the first electrode and the second electrode is configured to deliverradio frequency (RF) energy sufficient to ablate nerves in communicationwith the pulmonary system proximate the treatment site.

29. The treatment device of any of examples 22-28 wherein the balloon istransformable between a delivery state and a deployed state and wherein,in the deployed state, the balloon is sized and shaped to occlude thepulmonary blood vessel.

30. The treatment device of any of examples 22-29 wherein the balloon istransformable between a delivery state and a deployed state and wherein,in the deployed state, the balloon is sized and shaped to place thefirst electrode and second electrode in apposition with an inner wall ofthe pulmonary blood vessel.

31. A method, comprising:

-   -   intravascularly deploying a treatment device in a pulmonary        blood vessel of a human patient at a treatment site, wherein the        treatment device includes an elongated shaft, and first and        second electrodes;    -   ablating target nerves in communication with the pulmonary        system via radio frequency (RF) energy delivered from the first        electrode and/or the second electrode;    -   before ablation, stimulating the nerves in communication with        the pulmonary system near the treatment site and recording the        resulting nerve activity; and    -   after ablation, stimulating the nerves and recording the        resulting nerve activity.

32. The method of example 31, further comprising confirming theeffectiveness of the ablation on the nerves based on the post-ablationrecording.

33. The method of example 31 or example 32 wherein stimulating thenerves in communication with the pulmonary system before and/or afterablation is performed by the first electrode and recording nerveactivity before and/or after ablation is performed with the secondelectrode.

34. The method of any of examples 31-33 wherein:

-   -   stimulating the nerves in communication with the pulmonary        system before and after ablation comprises providing bipolar        stimulation to the nerves; and    -   recording nerve activity before and after ablation comprises        providing bipolar recording of the nerve activity with the        second electrode, wherein the second electrode is distal to the        first electrode.

35. The method of any of examples 31-34 wherein:

-   -   stimulating the nerves in communication with the pulmonary        system before and/or after ablation comprises delivering a        plurality of stimulus pulses with the first electrode; and    -   recording nerve activity before and after ablation is performed        by the second electrode, wherein recording comprises recording        an electrogram of the second electrode and that corresponds to        the nerve activity resulting from the corresponding stimulus        pulses.

36. The method of any of examples 31-35 wherein deploying the treatmentdevice includes deploying the first electrode proximal to the secondelectrode, wherein the first and second electrodes each comprise a loopelectrode.

37. The method of any of examples 31-36 wherein deploying the treatmentdevice in the pulmonary blood vessel comprises deploying the firstelectrode proximal to the second electrode.

38. The method of any of examples 31-37 wherein the treatment devicefurther includes a balloon at a distal portion of the shaft and thefirst and second electrodes are positioned on an outer surface of theballoon, and wherein deploying the treatment device in the pulmonaryblood vessel comprises inflating the balloon within a pulmonary artery,wherein the inflated balloon contacts an inner wall of the pulmonaryartery.

39. The method of any of examples 31-38 wherein the treatment devicefurther includes a balloon at a distal portion of the shaft and thefirst and second electrodes are positioned on an outer surface of theballoon, and wherein deploying the treatment device in the pulmonaryblood vessel comprises inflating the balloon within a pulmonary artery,wherein the inflated balloon, the first electrode, and the secondelectrode contact an inner wall of the pulmonary artery.

40. The method of any of examples 31-39 wherein:

-   -   stimulating nerves after ablation and recording the resulting        nerve activity is performed after delivering a first cycle of        ablation to nerves in communication with the pulmonary system;        and    -   the method further comprises delivering a second cycle of        ablation to nerves in communication with the pulmonary system        with the first and/or second electrodes when the recorded        post-ablation nerve activity from the first cycle is above a        predetermined threshold.

41. The method of any of examples 31-40 wherein recording nerve activitybefore and after ablation comprises providing bipolar recording of thenerve activity with the second electrode, wherein the second electrodeis distal to the first electrode.

42. The method of any of examples 31-40 wherein recording nerve activitybefore and after ablation is performed by the second electrode, whereinrecording comprises recording an electrogram of the second electrode andthat corresponds to the nerve activity resulting from the correspondingstimulus pulses.

43. The method of any of examples 31-42 further comprising delivering asecond cycle of ablation to nerves in communication with the pulmonarysystem with the first and/or second electrodes when the recordedpost-ablation nerve activity from the first cycle is above apredetermined threshold.

44. A method, comprising:

-   -   intravascularly deploying a treatment device in a pulmonary        blood vessel of a human patient at a treatment site, wherein the        treatment device includes an elongated shaft and first and        second electrodes at a distal portion of the shaft;    -   monitoring neural activity associated with target nerves in        communication with the pulmonary system near the treatment site;    -   ablating the target nerves via radio frequency (RF) energy        delivered from the first electrode and/or the second electrode;        and    -   determining a location of the target nerves in communication        with the pulmonary system before ablating the target nerves        and/or an extent of ablation of the target nerves after ablation        based on information obtained in the monitoring step.

45. The method of example 44 wherein monitoring neural activityassociated with the target nerves in communication with the pulmonarysystem comprises inducing neural activity associated with the targetnerves and recording the neural activity at the target nerves.

46. The method of example 44 wherein inducing the neural activitycomprises stimulating the target nerves in communication with thepulmonary system.

47. A method, comprising:

-   -   intravascularly deploying a treatment device in a pulmonary        blood vessel of a human patient at a treatment site;    -   ablating nerves in communication with the pulmonary system via        the treatment device; and    -   recording activity of the nerves in communication with the        pulmonary system.

48. The method of example 47 wherein the treatment device comprises anelongated shaft and first and second electrodes at a distal portion ofthe shaft.

49. The method of example 48 wherein ablating nerves in communicationwith the pulmonary system via the treatment device comprises deliveringradio frequency (RF) energy from the first electrode and/or the secondelectrode to tissue of the pulmonary blood vessel.

50. The method of example 48 wherein ablating nerves in communicationwith the pulmonary system via the treatment device comprises deliveringone or more chemicals to tissue of the pulmonary blood vessel.

51. The method of example 50 wherein ablating nerves in communicationwith the pulmonary system via the treatment device comprises deliveringethanol to tissue of the pulmonary blood vessel.

52. The method of example 48 wherein the treatment device furthercomprises a balloon at a distal portion of the shaft and the first andsecond electrodes are located on an outer surface of the balloon.

53. The method of example 48 wherein the treatment device furthercomprises a distal helical portion including the first and secondelectrodes.

54. The method of any one of examples 47-53 wherein recording activityof the nerves in communication with the pulmonary system comprisesrecording the activity after ablation of the nerves to confirm theeffectiveness of the ablation.

55. The method of any one of examples 47-54, further comprisingstimulating the nerves in communication with the pulmonary system beforeand/or after ablation is performed.

56. The method of example 47 wherein:

-   -   the treatment device comprises a first electrode and a second        electrode;    -   the method further comprises stimulating the nerves in        communication with the pulmonary system before and/or after        ablation by providing bipolar stimulation to the nerves; and    -   recording nerve activity comprises providing bipolar recording        of the nerve activity with the second electrode, wherein the        second electrode is distal to the first electrode.

57. The method of example 47 wherein:

-   -   the treatment device comprises a first electrode and a second        electrode;    -   the method further comprises stimulating the nerves in        communication with the pulmonary system before and/or after        ablation by delivering a plurality of stimulus pulses with the        first electrode; and    -   recording nerve activity is performed by the second electrode,        wherein recording comprises recording an electrogram of the        second electrode and that corresponds to the nerve activity        resulting from the corresponding stimulus pulses.

58. The method of example 47 wherein the treatment device comprises afirst electrode and a second electrode.

59. The method of example 58, further comprising stimulating the nervesin communication with the pulmonary system with the first electrodebefore and/or after ablation is performed and recording nerve activitywith the second electrode before and/or after ablation is performed.

60. The method of example 58 wherein deploying the treatment deviceincludes deploying the first electrode proximal to the second electrode,wherein the first and second electrodes each comprise a loop electrode.

61. The method of example 58 wherein deploying the treatment device inthe pulmonary blood vessel comprises deploying the first electrodeproximal to the second electrode.

62. The method of example 47 wherein the treatment device comprises aballoon and wherein deploying the treatment device in the pulmonaryblood vessel comprises inflating the balloon within a pulmonary artery,wherein the inflated balloon contacts an inner wall of the pulmonaryartery.

63. The method of example 47 wherein the treatment device comprises aballoon and wherein deploying the treatment device in the pulmonaryblood vessel comprises inflating the balloon within a pulmonary artery,wherein the inflated balloon, the first electrode, and the secondelectrode contact an inner wall of the pulmonary artery.

64. The method of example 55 wherein:

-   -   stimulating the nerves and recording the resulting nerve        activity is performed after delivering a first cycle of ablation        to nerves in communication with the pulmonary system; and    -   the method further comprises delivering a second cycle of        ablation to nerves in communication with the pulmonary system        when the recorded post-ablation nerve activity from the first        cycle is above a predetermined threshold.

65. The method of example 47 wherein the pulmonary blood vesselcomprises a pulmonary artery.

IV. Conclusion

Although many of the embodiments are described below with respect tosystems, devices, and methods for PN, the technology is applicable toother applications such as modulation of other nerves that communicatewith the renal system, modulation of peripheral nerves, and/ortreatments other than neuromodulation. Any appropriate site within thebody may be modulated or otherwise treated including, for example, thepulmonary inflow tract, pulmonary veins, pulmonary arteries, the carotidartery, renal arteries and branches thereof. In some embodiments,cardiac tissue (e.g., the left and/or right atrium of the heart) may bemodulated (e.g., to modulate electrical signals). Moreover, as furtherdescribed herein, while the technology may be used in helical or spiralneuromodulation devices, it may also be used in non-helical ornon-spiral neuromodulation devices as appropriate. Furthermore, otherembodiments in addition to those described herein are within the scopeof the technology. For example, in some embodiments the therapeuticassembly can include an expandable basket structure having one or moreenergy delivery elements positioned on the arms of the basket.Additionally, several other embodiments of the technology can havedifferent configurations, components, or procedures than those describedherein. A person of ordinary skill in the art, therefore, willaccordingly understand that the technology can have other embodimentswith additional elements, or the technology can have other embodimentswithout several of the features shown and described above with referenceto FIGS. 1-29.

Although many embodiments of the present technology are described foruse in an intravascular approach, it is also possible to use thetechnology in a non-vascular approach, such as a cutaneous and/ortranscutaneous approach to the nerves that innervate the pulmonarysystem. For example, the vagal and phrenic nerves may lie outside thelungs (e.g., in the neck region and/or in the inlet to the thoraciccavity) at various locations that may render them amenable to access viacutaneous puncture or to transcutaneous denervation. As such, devicesand/or methods described herein may be used to effect modulation ofvagal and/or phrenic nerves from within a carotid vein and/or a jugularvein. Neuromodulation at one or both of those locations may be effective(e.g., may provide a therapeutically beneficial effect with respect totreating pulmonary hypertension).

The above detailed descriptions of embodiments of the technology are notintended to be exhaustive or to limit the technology to the precise formdisclosed above. Although specific embodiments of, and examples for, thetechnology are described above for illustrative purposes, variousequivalent modifications are possible within the scope of thetechnology, as those skilled in the relevant art will recognize. Forexample, while steps are presented in a given order, alternativeembodiments may perform steps in a different order. The variousembodiments described herein may also be combined to provide furtherembodiments.

From the foregoing, it will be appreciated that specific embodiments ofthe technology have been described herein for purposes of illustration,but well-known structures and functions have not been shown or describedin detail to avoid unnecessarily obscuring the description of theembodiments of the technology. Where the context permits, singular orplural terms may also include the plural or singular term, respectively.

Moreover, unless the word “or” is expressly limited to mean only asingle item exclusive from the other items in reference to a list of twoor more items, then the use of “or” in such a list is to be interpretedas including (a) any single item in the list, (b) all of the items inthe list, or (c) any combination of the items in the list. Additionally,the term “comprising” is used throughout to mean including at least therecited feature(s) such that any greater number of the same featureand/or additional types of other features are not precluded. It willalso be appreciated that specific embodiments have been described hereinfor purposes of illustration, but that various modifications may be madewithout deviating from the technology. Further, while advantagesassociated with certain embodiments of the technology have beendescribed in the context of those embodiments, other embodiments mayalso exhibit such advantages, and not all embodiments need necessarilyexhibit such advantages to fall within the scope of the technology.Accordingly, the disclosure and associated technology can encompassother embodiments not expressly shown or described herein.

1-40. (canceled) 41: A non-occlusive catheter comprising: an elongatedshaft comprising a proximal portion and a distal portion; and atherapeutic assembly carried by the distal portion, the therapeuticassembly comprising: a therapeutic element carried by the distalportion; and at least one expandable balloon attached to the distalportion, wherein, when in a deployed state, the at least one expandableballoon is configured to position the therapeutic element at a desireddistance relative to a vessel wall and allow blood flow past the atleast one expandable balloon. 42: The non-occlusive catheter of claim41, wherein the at least one expandable balloon comprises a firstballoon and a second balloon radially adjacent to the first balloon. 43:The non-occlusive catheter of claim 42, wherein the therapeutic elementis within the first balloon. 44: The non-occlusive catheter of claim 41,wherein the at least one expandable balloon comprises a donut-shapedexpandable balloon, which, in the deployed state, defines alongitudinally extending opening through which blood can flow. 45: Thenon-occlusive catheter of claim 44, wherein the longitudinally extendingopening radially centrally located. 46: The non-occlusive catheter ofclaim 44, wherein the therapeutic element is within the donut-shapedexpandable balloon. 47: The non-occlusive catheter of claim 41, whereinthe therapeutic element comprises an energy delivery element. 48: Thenon-occlusive catheter of claim 47, wherein the energy delivery elementcomprises at least one of a radiofrequency electrode, a microwavetransducer, an optical transducer, an ultrasound transducer, heatingelement, or a cryotherapeutic element. 49: The non-occlusive catheter ofclaim 48, wherein the therapeutic element comprises a substance deliveryfeature configured to deliver a neuromodulation chemical. 50: Thenon-occlusive catheter of claim 49, wherein the neuromodulation chemicalcomprises guanethidine, an alcohol, a phenol, a neurotoxin or ananesthetic agent. 51: The non-occlusive catheter of claim 41, whereinthe distal portion and the therapeutic assembly are configured to bepositioned in a pulmonary vessel. 52: A method comprising: delivering atherapeutic assembly carried by a distal portion of an elongated shaftof a non-occlusive catheter within a blood vessel; expanding at leastone expandable balloon attached to the distal portion to a deployedstate, wherein, when in the deployed state, the at least one expandableballoon is configured to position a therapeutic element of thetherapeutic assembly at a desired distance relative to a vessel wall andallow blood flow past the at least one expandable balloon; anddelivering therapy to at least one nerve adjacent the blood vessel usingthe therapeutic element. 53: The method of claim 52, wherein the atleast one expandable balloon comprises a first balloon and a secondballoon radially adjacent to the first balloon, and wherein expanding atleast one expandable balloon comprises expanding the first balloon andthe second balloon. 54: The method of claim 53, wherein the therapeuticelement is within the first balloon. 55: The method of claim 52, whereinthe at least one expandable balloon comprises a donut-shaped expandableballoon, and wherein expanding at least one expandable balloon comprisesexpanding the donut-shaped expandable balloon to contact the vessel walland define a longitudinally extending opening through which blood canflow. 56: The method of claim 55, wherein the longitudinally extendingopening radially centrally located. 57: The method of claim 55, whereinthe therapeutic element is within the donut-shaped expandable balloon.58: The method of claim 52, wherein the therapeutic element comprises anenergy delivery element, and wherein delivering therapy to the at leastone nerve adjacent the blood vessel comprises delivery energy to the atleast one nerve adjacent the blood vessel. 59: The method of claim 58,wherein the energy delivery element comprises at least one of aradiofrequency electrode, a microwave transducer, an optical transducer,an ultrasound transducer, heating element, or a cryotherapeutic element.60: The method of claim 59, wherein the therapeutic element comprises asubstance delivery feature configured to deliver a neuromodulationchemical, and wherein delivering therapy to at least one nerve adjacentthe blood vessel comprises delivering the neuromodulation chemical tothe at least one nerve adjacent the blood vessel.